IGIB finds a protein with better precision in gene-editing – The Hindu

Researchers at the Delhi-based Institute of Genomics and Integrative Biology (CSIR-IGIB) have discovered a protein variant from a different species of bacteria that can edit the DNA with very high precision. In the tool now commonly used for editing disease-causing mutations in DNA (CRISPR-Cas9), the Cas9 protein behaves like a molecular scissors that cuts the DNA at a specific location and inserts a foreign piece of DNA to correct the mutation that causes the disease.

In addition to binding to the intended target on the DNA, the commonly used Cas9 protein from Strepotococcus pyogenes bacteria (SpCas9) and its engineered derivative tend to potentially bind to DNA at multiple unintended sites thereby leading to unnecessary alterations in the DNA.

The researchers found their new Cas9 protein, which binds and cuts the DNA, was able to correct sickle cell anaemia mutation in patient-derived stem cells. The protein (FnCas9) used by the researchers to edit the DNA is derived from a bacterium Francisella novicida.

The Cas9 protein is supposed to bind to the DNA only when there is a perfect match between the DNA and the protein, thus reducing the chances of the protein binding at non-target sites on the DNA. But even when three mismatches exist between the protein and the DNA, the currently used SpCas9 protein binds and cleaves the DNA. In contrast, the team led by Debojyoti Chakraborty from IGIB found the new FnCas9 protein showed negligible binding when there exists more than one mismatch in the target DNA. The results were published in the journal Proceedings of the National Academy of Sciences (PNAS).

The high specificity of the new FnCas9 protein arises due to reduced affinity to bind to DNA when there is even a single mismatch. And when there is more than one mismatch, complete absence of binding of the protein to the DNA is seen in many cases, says Dr. Chakraborty.

If the Cas9 protein remains bound to DNA at mismatched locations for a long time, there is a possibility that it might cut the DNA at these locations. Also, if it remains bound to DNA, the protein might block the transcription (which is the first step in gene expression) at that location. And if Cas9 is bound at multiple unintended sites then the transcription machinery gets stalled and the expression of genes at these locations might be altered, Dr. Chakraborty explains.

In nature, DNA often gets damaged and is routinely repaired through one of the two pathways. In the case of the homology-directed repair (HDR) pathway, which is relatively less error-prone, matching sequences are used to repair the DNA. The FnCas9 protein was found to increase the HDR repair rate fourfold compared to the widely used SpCas9, says Deepanjan Paul from CSIR-IGIB and one of the first authors of the paper.

The researchers tested the precision of binding and cleavage at the desired sites on the DNA using mouse cell lines (embryonic stem cells and brain cells), human kidney cell lines and induced pluripotent stem cells (iPSc). In the case of human iPS cells, the FnCas9 protein was found to bind to the DNA at the specific site, cut and repair the sickle cell anaemia mutation.

The correction process is the same for any disease-causing mutation and so our FnCas9 protein should theoretically correct any mutation in the DNA. The efficiency might vary, so we must test it for each disorder, says Dr. Chakraborty.

The efficiency of any Cas9 protein delivery as well the ability to correct mutations is generally low in the case of iPS cells. The efficiency of correction is about 1.6%. Though the efficiency to correct mutations is low in iPS cells, the corrected cells can be isolated, multiplied and converted (differentiated) into haematopoietic stem cells. Once differentiated into haematopoietic stem cells, they can be transfused into patients.

Differentiating iPS cells into haematopoietic stem cells is not trivial. Plenty of experimental work is under way to make it efficient for clinical translation, says Dr. Chakraborty.

Recalling how he started working on FnCas9 protein for genome editing, Dr. Chakraborty recalls that he was looking for a Cas9 protein which can target RNA instead of DNA. There was one study that reported that FnCas9 could potentially target viral RNA. We were not able to target RNA using FnCas9 proteins. So we started to investigate whether it can target DNA as well since it was not known if FnCas9 can be used for precise gene correction. We found that not only does it target the DNA but does so with very high specificity, he says.

We are now proceeding for preclinical studies to establish the efficacy of FnCas9 protein for genome-wide binding and targeting using patient-derived cells and mouse models, he says.

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IGIB finds a protein with better precision in gene-editing - The Hindu

Novel Cell Sorting and Separation Market: Focus on Acoustophoresis, Buoyancy-activated, Dielectrophoresis, Magnetophoretics, Microfluidics,…

NEW YORK, Oct. 1, 2019 /PRNewswire/ --

INTRODUCTIONAdvances in the fields of cell biology and regenerative medicine have led to the development of various cell-based therapies, which, developers claim, possess the potential to treat a variety of clinical conditions. In 2018, it was reported that there were more than 1,000 clinical trials of such therapies, being conducted across the globe by over 900 industry players. Moreover, the total investment in the aforementioned clinical research efforts was estimated to be around USD 13 billion. Given the recent breakthroughs in clinical testing and the discovery of a variety of diagnostic biomarkers, the isolation of one or multiple cell types from a heterogenous population has not only become simpler, but also an integral part of modern clinical R&D. The applications of cell separation technologies are vast, starting from basic research to biological therapy development and manufacturing. However, conventional cell sorting techniques, including adherence-based sorting, membrane filtration-based sorting, and fluorescence- and magnetic-based sorting, are limited by exorbitant operational costs, time-consuming procedures, and the need for complex biochemical labels. As a result, the use of such techniques has, so far, been restricted in the more niche and emerging application areas.

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Over the years, extensive research in the field of flow cytometry has enabled the development of a variety of novel technologies that are capable of efficiently isolating cells from tissue samples and / or heterogenous cell populations. In fact, since 2014, over 3,000 patents were reported to have been filed / granted related to such advanced techniques, indicating the rapid pace of innovation in this domain. Developers of the aforementioned technologies claim that these new techniques offer numerous benefits, including fast and precise cell sorting, reduced sample requirement, improved portability, reduced risk to cell viability, and negligible need for expensive biochemical / magnetic labels. Moreover, they have been shown to be compatible for use across a myriad of applications, including research studies (bacteriology, immunology, stem cell research, and viral titering and infectivity), biomedical diagnostics (circulating tumor cell detection, in vitro fertilization, and non-invasive prenatal diagnosis), biological therapy-related process operations (bio-banking, drug discovery, sample preparation, single cell sequencing, and tumor cell characterization), and cell-based therapeutics (B- or T-cell immunotherapies). Consequently, these techniques have captured the interest of several stakeholders in the biopharmaceutical industry. It is also worth highlighting that stakeholders in this domain have received significant support from both private and public investors.

SCOPE OF THE REPORTThe 'Novel Cell Sorting and Separation Market: Focus on Acoustophoresis, Buoyancy-activated, Dielectrophoresis, Magnetophoretics, Microfluidics, Optoelectronics, Photoacoustics, Traceless Affinity and Other Technologies, 2019-2030' report features an extensive study of the current landscape and future outlook of the growing market for novel cell sorting and separation technologies (beyond conventional methods). The study presents detailed analyses of cell sorters, cell isolation kits, and affiliated consumables and reagents, that are based on the aforementioned technologies.

Amongst other elements, the report features: A detailed assessment of the current market landscape, featuring a comprehensive list of over 220 innovative cell sorters, cell isolation kits, and affiliated consumables and reagents, along with information on their respective specifications (such as size, weight, cell flow rate, cell sort rate, cell analysis rate, cell purity and viability, process time, and operating temperature and pressure), cell sorting technology (acoustophoresis, buoyancy-activated, dielectrophoresis, magnetophoretics, microfluidics, optoelectronics, photoacoustics, traceless affinity, and others), type of cell (animal cells, cancer cells, immune cells, microbial cells, red blood cells / platelets, stem cells, and others), cell separation approach (positive selection, negative selection and depletion), basis for separation (cell morphology and physiology, cell size and density, surface biomarkers, surface charge and adhesion, and others), and end use / application (research studies, biomedical diagnostics, biological therapy-related process operations, and cell-based therapeutics). An insightful company competitiveness analysis, taking into consideration the supplier power (based on size of employee base and experience in this segment of the industry) and portfolio-related parameters, such as number of products offered, number of target cells, end use(s) / application(s), and key product specification(s). Comprehensive profiles of key industry players (shortlisted on the basis of company competitiveness analysis scores) that are currently offering novel cell sorters / consumables and cell isolation kits, featuring an overview of the company, its financial information (if available), and a detailed description of its proprietary product(s). Each profile also includes a list of recent developments, highlighting the key achievements, partnership activity, and the likely strategies that may be adopted by these players to fuel growth in the foreseen future. An in-depth analysis of the patents that have been filed / granted related to novel cell sorting and separation technologies, since 2014. It highlights the key trends associated with these patents, across patent type, regional applicability, CPC classification, emerging focus areas, leading industry players (in terms of number of patents filed / granted), and current intellectual property-related benchmarks and valuation. A detailed publication analysis of more than 200 peer-reviewed, scientific articles that have been published since 2014, highlighting the research focus within the industry. It also highlights the key trends observed across the publications, including information on innovative technologies, potential application areas, target disease indications, type of cell, and analysis based on various relevant parameters, such as year of publication, and most popular journals (in terms of number of articles published in the given time period) within this domain. An analysis of the partnerships that have been established in the domain, in the period 2014-Q1 2019, covering R&D collaborations, licensing agreements, distribution agreements, mergers / acquisitions, asset purchase agreements, product development agreements, product utilization agreements, and other relevant deals. An analysis of the investments made at various stages of development, such as seed financing, venture capital financing, debt financing, grants / awards, capital raised from IPOs and subsequent offerings, by companies that are engaged in this field. An analysis to estimate the likely demand for novel cell sorting products and solutions across key application areas, including research studies, clinical diagnostics, cell-based therapeutics, and other applications, in different global regions for the period 2019-2030.

One of the key objectives of the report was to understand the primary growth drivers and estimate the future size of the novel cell sorting and separation market. Based on multiple parameters, such as potential application areas, likely adoption rate and expected pricing, we have provided an informed estimate on the likely evolution of the market, over the period 2019-2030. In addition, we have provided the likely distribution of the current and forecasted opportunity across [A] potential application areas (research studies, clinical diagnostics, cell-based therapeutics, and other applications), [B] end users (academic institutes, clinical testing labs, hospitals, and commercial organizations), [C] type of offering (cell sorters, and consumables and isolation kits), [D] cell sorting technology (buoyancy-activated, magnetophoretics, microfluidics, optoelectronics, and other advanced technologies), [E] type of cell (adult stem cells, CAR-T cells, circulating fetal cells, circulating tumor cells, dendritic cells, embryonic stem cells, insect cells, induced pluripotent stem cells, microbial cells, sperm cells, TCR cells, TILs, and tumor cells / cancer cells), [F] size of cell (< 5 m, 5-10 m, 10-15 m, 15-25 m, and > 25 m), and [G] key geographical regions (North America, Europe and Asia-Pacific). In order to account for the uncertainties associated with some of the key parameters and to add robustness to our model, we have provided three market forecast scenarios portraying the conservative, base and optimistic tracks of the industry's evolution.

The opinions and insights presented in this study were also influenced by discussions conducted with multiple stakeholders in this domain. The report features detailed transcripts of interviews held with the following individuals (in alphabetical order of organization names): John Younger (Co-founder and Chief Technology Officer, Akadeum Life Sciences) Sean Hart (Chief Executive Officer and Chief Scientific Officer, LumaCyte) Soohee Cho (Product Manager, Namocell)

All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.

RESEARCH METHODOLOGYThe data presented in this report has been gathered via secondary and primary research. For all our projects, we conduct interviews with experts in the area (academia, industry and other associations) to solicit their opinions on emerging trends in the market. This is primarily useful for us to draw out our own opinion on how the market will evolve across different regions and technology segments. Where possible, the available data has been checked for accuracy from multiple sources of information.

The secondary sources of information include Annual reports Investor presentations SEC filings Industry databases News releases from company websites Government policy documents Industry analysts' views

While the focus has been on forecasting the market till 2030, the report also provides our independent view on various non-commercial trends emerging in the industry. This opinion is solely based on our knowledge, research and understanding of the relevant market gathered from various secondary and primary sources of information.

CHAPTER OUTLINESChapter 2 is an executive summary of the insights captured in our research. It offers a high-level view on the likely evolution of novel cell sorting and separation market in the mid-long term.

Chapter 3 is an introductory chapter that presents a general overview of cell sorting and separation, including a brief history of development, and information on the basic components and principle of operation of a cell sorter. Further, it features a detailed discussion on conventional cell separation techniques and the various challenges associated with their use across different application areas. The chapter also includes detailed sections on the novel cell sorting and separation technologies (such as acoustophoresis, buoyancy-activated, dielectrophoresis, magnetophoretics, microfluidics, optoelectronics, photoacoustics, traceless affinity, and others), highlighting their advantages and challenges. Further, it features a discussion on the key growth drivers and roadblocks related to modern cell sorting technologies, as well as upcoming trends that the field is expected to witness in the coming years.

Chapter 4 includes information on more than 220 innovative cell sorters, cell isolation kits, and affiliated consumables and reagents, along with details on their respective specifications (such as size, weight, cell flow rate, cell sort rate, cell analysis rate, cell purity and viability, process time, and operating temperature and pressure), cell sorting technology (acoustophoresis, buoyancy-activated, dielectrophoresis, magnetophoretics, microfluidics, optoelectronics, photoacoustics, traceless affinity, and others), type of cell (animal cells, cancer cells, microbial cells, red blood cells / platelets, stem cells, and others), cell separation approach (positive selection, negative selection and depletion), basis for separation (cell morphology and physiology, cell size and density, surface biomarkers, surface charge and adhesion, and others), and end use / application (research studies, biomedical diagnostics, biological therapy-related process operations, and cell-based therapeutics). The chapter also highlights the contributions of various companies engaged in this domain, presenting detailed analyses, based on their year of establishment, size of employee base, geographical presence, and type of offering.

Chapter 5 features an insightful competitiveness analysis of the companies engaged in novel cell sorting and separation domain, based on various parameters, such as number of products offered, number of target cells, end use(s) / application(s), and key product specification(s). In the chapter, stakeholder entities have been plotted on a 2X2 matrix, featuring a company's Supplier Power (based on size of employee base and experience in this segment of the industry) and Company Competitiveness as the two axes.

Chapter 6 includes elaborate profiles of key industry players (shortlisted on the basis of company competitiveness analysis scores) that are offering novel cell sorters / sorting technologies; each profile features an overview of the company, its financial information (if available), and a detailed description of its proprietary product(s). Each profile also includes a list of recent developments, highlighting the key achievements, partnership activity, and the likely strategies that may be adopted by these players to fuel growth, in the foreseen future.

Chapter 7 includes detailed profiles of key industry players (shortlisted on the basis of company competitiveness analysis scores) that are offering novel consumables and cell isolation kits; each profile features an overview of the company, its financial information (if available), and a detailed description of its proprietary product(s). Each profile also includes a list of recent developments, highlighting the key achievements, partnership activity, and the likely strategies that may be adopted by these players to fuel growth, in the foreseen future.

Chapter 8 provides an in-depth patent analysis to provide an overview of how the industry is evolving from the R&D perspective. For this analysis, we considered those patents that have been filed / granted related to novel cell sorting and separation technologies, since 2014. The analysis also highlights the key trends associated with these patents, across patent type, regional applicability, CPC classification, emerging focus areas, leading industry players (in terms of number of patents filed / granted), and current intellectual property-related benchmarks and valuation.

Chapter 9 presents a detailed publication analysis of more than 200 peer-reviewed, scientific articles that have been published since 2014, highlighting the research focus within the industry. It also highlights the key trends observed across the publications, including information on innovative technologies, potential application areas, target disease indications, type of cell, and analyses based on various relevant parameters, such as year of publication, and most popular journals (in terms of number of articles published in the given time period) within this domain.

Chapter 10 features an elaborate analysis and discussion of partnerships / collaborations that have been established in this domain in the period 2014-Q1 2019. It includes a brief description of various types of partnership models (such as R&D collaborations, licensing agreements, distribution agreements, mergers / acquisitions, asset purchase agreements, product development agreements, product utilization agreements, and others) that have been employed by stakeholders within this domain. It also consists of a schematic representation showcasing the players that have established the maximum number of alliances related to novel cell sorting and separation technologies. Furthermore, we have provided a world map representation of all the deals inked in this field, highlighting those that have been established within and across different continents.

Chapter 11 provides information on funding instances and investments that have been made within the novel cell sorting and separation domain. The chapter includes details on various types of investments (such as seed financing, venture capital financing, debt financing, grants, capital raised from IPOs and subsequent offerings) received by companies in the period 2014-Q1 2019, highlighting the growing interest of the venture capital community and other strategic investors in this domain.

Chapter 12 provides an overview of the demand for novel cell sorting products and solutions across key application areas, including research studies, clinical diagnostics, cell-based therapeutics, and other applications, in the contemporary market. In order to estimate the aforementioned demand, we considered the number of ongoing / completed research studies, diagnostic tests and cell-based therapies under development across different geographies. We also estimated the likely adoption of such products and solutions across key application areas, over the period 2019-2030.

Chapter 13 features a comprehensive market forecast, highlighting the future potential of novel cell sorting and separation market till 2030, based on multiple parameters, such as potential application areas, likely adoption rate and expected pricing. In addition, we estimated the likely distribution of the current and forecasted opportunity across [A] potential application areas (research studies, clinical diagnostics, cell-based therapeutics, and other applications), [B] end users (academic institutes, clinical testing labs, hospitals, and commercial organizations), [C] type of offering (cell sorters, and consumables and isolation kits), [D] cell sorting technology (buoyancy-activated, magnetophoretics, microfluidics, optoelectronics, and other advanced technologies), [E] type of cell (adult stem cells, CAR-T cells, circulating fetal cells, circulating tumor cells, dendritic cells, embryonic stem cells, insect cells, induced pluripotent stem cells, microbial cells, sperm cells, TCR cells, TILs, and tumor cells / cancer cells), [F] size of cell (< 5 m, 5-10 m, 10-15 m, 15-25 m, and > 25 m), and [G] key geographical regions (North America, Europe and Asia-Pacific). We adopted a combination of top-down and bottom up approaches, backed by robust data and credible inputs from primary research, to estimate the likely size of the market, both in terms of value (USD billion) and volume (number of products).

Chapter 14 is a collection of executive insights of the discussions that were held with various key stakeholders in this market. The chapter provides a brief overview of the companies and details of interviews held with John Younger (Co-founder and Chief Technology Officer, Akadeum Life Sciences), Sean Hart (Chief Executive Officer and Chief Scientific Officer, LumaCyte), and Soohee Cho (Product Manager, Namocell).

Chapter 15 is a summary of the overall report. In this chapter, we have provided a list of key takeaways from the report, and expressed our independent opinion related to the research and analysis described in the previous chapters.

Chapter 16 is an appendix, which provides tabulated data and numbers for all the figures provided in the report.

Chapter 17 is an appendix, which contains the list of companies and organizations mentioned in the report.

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Fabry Heart Cells Grown in Lab Dish Give Hints to Cardiac Complications – Fabry Disease News

Heart cells derived from patients stem cells and grown in a lab dish can reveal important clues about the development of heart ailments associated with Fabry disease.

The study, A Human Stem Cell Model of Fabry Disease Implicates LIMP-2 Accumulation in Cardiomyocyte Pathology, was published in Stem Cell Reports.

Fabry is a rare genetic disorder caused by mutations in the GLA gene. Located on the X chromosome, the gene provides instructions for the production of an enzyme called alpha-galactosidase A (alpha-GAL A).

These mutations typically affect the activity of alpha-GAL A, leading to the accumulation of a type of fat called globotriaosylceramide (GL-3) in different tissues and organs, including the heart, kidneys and nervous system, gradually compromising their normal function.

For this reason, most Fabry patients develop heart disease over the course of their lives, which may progress to heart failure, the most common cause of death among people living with the disorder.

A major obstacle for advancing therapy for patients with [Fabry disease] is the knowledge gap between the direct molecular consequences of alpha-GAL A deficiency in CMs [cardiomyocytes, or heart cells] and the cascade of events driving disease in the heart; the inaccessibility of CMs from patients precludes adequate investigation of these events, especially at early stages, the investigators wrote.

In a previous study, researchers describe the generation of induced pluripotent stem cells (iPSCs) from Fabry patients carrying nonsense mutations in the GLA gene. This gave them the possibility, for the first time, to study the impact of alpha-GAL A deficiency on heart cells derived from patients iPSCs grown in a lab dish.

(iPSCs are fully matured cells that are reprogrammed back to a stem cell state, where they are able to grow into any type of cell. A nonsense mutation is a mutation in which the alteration of a single nucleotide (the building blocks of DNA) makes proteins shorter.)

Investigators from Sanofi, in collaboration with researchers at the University of Manchester, further investigated the properties of heart cells derived from patients iPSCs. Their aim was to discover more clues about the molecular mechanisms involved in the development of heart disease linked to Fabry.

Functional and structural characterization experiments revealed that heart cells from Fabry patients had higher levels of GL-3, and showed a series of abnormalities in the way they responded to electrical stimuli and in how they regulated their calcium usage, compared to heart cells from healthy people serving as controls. Calcium is essential to coordinate the hearts function by contributing to the electrical signals involved in heart muscle contraction.

When researchers analyzed the protein contents of heart cells grown in a lab dish, they found these cells produced more than 5,500 different proteins. This analysis also showed that compared to controls, heart cells from Fabry patients produced large amounts of lysosomal membrane protein 2 (LIMP-2) and heat shock-related 70 kDa protein 2 (HSPA2/HSP70-2).

(LIMP-2 is a protein normally found on the membrane of lysosomes small structures within cells that accumulate, digest, and recycle materials that regulates their transport within cells; HSPA2/HSP70-2 is a protein involved in cellular quality control, participating in the folding of other proteins and targeting abnormal proteins for degradation.)

Heart cells from Fabry patients released high amounts of cathepsin F, a protein that helps breakdown materials being transported inside lysosomes, as well as HSPA2/HSP70-2. As expected, when researchers corrected the genetic mutation associated with Fabry in heart cells derived from patients iPSCs, all these defects were reversed.

To confirm the validity of these proteins as Fabry biomarkers, researchers then forced healthy heart cells to produce high amounts of LIMP-2. They discovered this also triggered the release of large amounts of cathepsin F and HSPA2/HSP70-2, resulting in a massive accumulation of vacuoles (enclosed compartments filled with water and other substances) inside cells.

In summary, our study has shown the power of the iPSC model to reveal early functional changes and the development of a distinctive biomarker expression profile in [Fabry disease] CMs. These biomarkers may be of utility in drug screening and in elucidating the earliest pathological events and cascades in [Fabry disease] cells. Quantification in patient plasma and urine samples will be an important next step toward validating their relevance in patients, the researchers wrote.

A better understanding of these mechanisms will no doubt accelerate the development of more effective and increasingly personalized therapies for patients, they added.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

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Fabry Heart Cells Grown in Lab Dish Give Hints to Cardiac Complications - Fabry Disease News

Global Induced Pluripotent Stem Cells (iPSCs) Market 2019 Analysis & Forecast Report 2024 – Analytics News

According to this study, over the next five years the Induced Pluripotent Stem Cells (iPSCs) market will register a 12.7% CAGR in terms of revenue, the global market size will reach US$ 13910 million by 2024, from US$ 11320 million in 2019. In particular, this report presents the global market share (sales and revenue) of key companies in Induced Pluripotent Stem Cells (iPSCs) business, shared in Chapter 3.

This report presents a comprehensive overview, market shares, and growth opportunities of Induced Pluripotent Stem Cells (iPSCs) market by product type, application, key manufacturers and key regions and countries.

Research report is delivering the complete study of different factors for market growth and various factors are showing the significant responsibility in the growth of market during the forecast period. Hence, report is competently delivering the comprehensive study about the revenue considering share, production and price. Thus offering the outline of different segmentations about region, taking into the consideration the production details and revenue impacting the growth.

Request a sample report here: https://www.orbisresearch.com/contacts/request-sample/3685986

This study considers the Induced Pluripotent Stem Cells (iPSCs) value and volume generated from the sales of the following segments:

Segmentation by product type: breakdown data from 2014 to 2019, in Section 2.3; and forecast to 2024

Human iPSCsMouse iPSCs

Human iPSCs had a market share of 89% in 2018, followed by Mouse iPSCs.

Segmentation by application: breakdown data from 2014 to 2019, in Section 2.4; and forecast to 2024

Academic ResearchDrug Development and DiscoveryToxicity ScreeningRegenerative Medicine

Academic Research is the largest segment of Induced Pluripotent Stem Cells (iPSCs) application,with a share of 32% in 2018.

This report also splits the market by region: Breakdown data in Chapter 4, 5, 6, 7 and 8.

AmericasUnited StatesCanadaMexicoBrazilAPACChinaJapanKoreaSoutheast AsiaIndiaAustraliaEuropeGermanyFranceUKItalyRussiaSpainMiddle East & AfricaEgyptSouth AfricaIsraelTurkeyGCC Countries

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The report also presents the market competition landscape and a corresponding detailed analysis of the major vendor/manufacturers in the market. The key manufacturers covered in this report: Breakdown data in in Chapter 3.

Fujifilm Holding Corporation (CDI)NcardiaAstellas Pharma IncFate Therapeutics, IncSumitomo Dainippon PharmaReproCELLPluricell BiotechCell Inspire Biotechnology

In addition, this report discusses the key drivers influencing market growth, opportunities, the challenges and the risks faced by key manufacturers and the market as a whole. It also analyzes key emerging trends and their impact on present and future development.

Research objectives

To study and analyze the global Induced Pluripotent Stem Cells (iPSCs) consumption (value & volume) by key regions/countries, product type and application, history data from 2014 to 2018, and forecast to 2024.

To understand the structure of Induced Pluripotent Stem Cells (iPSCs) market by identifying its various subsegments.

Focuses on the key global Induced Pluripotent Stem Cells (iPSCs) manufacturers, to define, describe and analyze the sales volume, value, market share, market competition landscape, SWOT analysis and development plans in next few years.

To analyze the Induced Pluripotent Stem Cells (iPSCs) with respect to individual growth trends, future prospects, and their contribution to the total market.

To share detailed information about the key factors influencing the growth of the market (growth potential, opportunities, drivers, industry-specific challenges and risks).

To project the consumption of Induced Pluripotent Stem Cells (iPSCs) submarkets, with respect to key regions (along with their respective key countries).

To analyze competitive developments such as expansions, agreements, new product launches, and acquisitions in the market.

To strategically profile the key players and comprehensively analyze their growth strategies.

Table of Contents

1 Scope of the Report1.1 Market Introduction1.2 Research Objectives1.3 Years Considered1.4 Market Research Methodology1.5 Economic Indicators1.6 Currency ConsideredContinued

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Blood Pressure and Prostate Treatment May Prevent or Slow Parkinson’s, Early Study Suggests – Parkinson’s News Today

People taking Hytrin (terazosin)or similar medications to treat high blood pressure and benign prostatic hyperplasiamay be less likely to develop Parkinsons disease, an early study suggests.

Parkinsons patients who use these medications may also see their disease progress more slowly and with fewer complications, its researchers report.

The study, Enhancing glycolysis attenuates Parkinsons disease progression in models and clinical databases, was published in the Journal of Clinical Investigation.

Hytrin is indicated for the treatment of non-cancerous prostate enlargement and high blood pressure (hypertension). The medication, available as a generic (terazosin), acts on the alpha-1 adrenergic receptor to block adrenalines action, relaxing smooth muscle in both the blood vessels and the prostate, allowing blood and urine, respectively, to flow more easily.

Experts agree that energy metabolism plays a central role in the molecular mechanism of neurodegenerative diseases like Parkinsons. In fact, problems in energy metabolism and low levels of cellular energy are common features of this disorder.

Hytrin has been shown to enhance the activity of a protein called phosphoglycerate kinase 1 (PGK1), which is involved in a critical energy-producing process known as glycolysis, where the simple sugar glucose is broken down by cells to produce energy. Boosting PGK1 activity increases the number of energy molecules, also known as ATP, within a cell.

Because low levels of ATP have been observed in Parkinsons, increasing the breakdown of glucose and hence cellular energy, in theory, may slow down or prevent the neurodegenerative processes underlying this disease.

Researchers at Capital Medical University in Beijing, decided to test this hypothesis and investigate whether increasing PGK1 activity levels would change the course of Parkinsons disease.

Hytrin was found to increase brain ATP levels and slow or prevent nerve cell loss in several models of Parkinsons (MPTP, rotenone and 6-OHDA-induced or genetic models): mice, rats, flies, and induced pluripotent stem cells. MPTP, rotenone and 6-OHDA are all neurotoxins that induce death of dopamine-producing neurons and mimic Parkinsons symptoms.

Treatment with this medication increased brain dopamine levels the chemical messenger that is present in low levels in the brains of Parkinsons patients and partially restored motor function in both mice and flies.

Importantly, boosting PGK1 activity was beneficial even when treatment was initiated after the onset of neurodegeneration, suggesting the modulation of this proteins function could help to slow Parkinsons progression.

Because Hytrin is prescribed for other diseases, scientists also studied two human databases the Parkinsons Progression Markers Initiative and the IBM Watson/Truven database looking for a possible Hytrin effect in relation to Parkinsons disease.

These two data sets included a total of 4,072 individuals on Hytrin, doxazosin, or alfuzosin. The latter two medications produce effects similar to those of Hytrin.

A retrospective analysis on both databases revealed that use of Hytrin and related agents slowed Parkinsons disease progression, reduced the number of neurodegeneration-related complications, and lessened the risk of a Parkinsons diagnosis, compared to people not using these medications.

These findings identify a protein and a pathway that might be targeted to slow or prevent neurodegeneration in PD [Parkinsons disease] and potentially other neurodegenerative diseases with altered energy balance, the researchers concluded.

Terazosin, available only by prescription, can cause dizziness and fainting because it lowers blood pressure.

With over three years of experience in the medical communications business, Catarina holds a BSc. in Biomedical Sciences and a MSc. in Neurosciences. Apart from writing, she has been involved in patient-oriented translational and clinical research.

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Blood Pressure and Prostate Treatment May Prevent or Slow Parkinson's, Early Study Suggests - Parkinson's News Today

Gene regulators work together for oversized impact on schizophrenia risk – National Institutes of Health

News Release

Monday, September 23, 2019

Modeled gene expression changes match those found in patients brains.

Researchers have discovered that gene expression regulators work together to raise an individuals risk of developing schizophrenia. Schizophrenia-like gene expression changes modeled in human neurons matched changes found in patients brains. The researchers, led by Kristen Brennand, of the Icahn School of Medicine at Mount Sinai, New York City, report on their findings in Nature Genetics. The work was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health.

Genome-wide association studies have revealed at least 143 chromosomal sites associated with risk for schizophrenia. However, individually, each of these sites can explain only a small fraction of the risk. Even when the effects of disease-linked rare genetic variants are factored in, most of schizophrenias known high inheritance remains unexplained. One possible clue: more than 40% of the suspect chromosomal sites contain regulators, called expression quantitative trait loci, or eQTLs, that govern the expression of multiple genes.

Individually, these gene regulators have a modest effect on the brain. Working in concert, they exert different and more significant effects on the brain effects that boost schizophrenia risk, explained David Panchision, chief of the Developmental Neurobiology Program at NIMH. Learning more about the downstream cellular and molecular effects of such synergy holds hope for advances in precision psychiatry and more personalized medicine.

To explore the role of these regulators, Brennand and colleagues studied them in induced neurons using a molecular modeling technology. This induced pluripotent stem cell method makes it possible to grow a persons unique neurons in a petri dish using stem cells derived from their skin cells. The researchers used the model to take a closer look at the downstream molecular consequences of gene expression changes known to occur in schizophrenia, and compared them with changes seen in postmortem brains and similarly modeled neurons of people with the illness.

The researchers experimentally mimicked the interaction of multiple risk genes thought to contribute to schizophrenia. They used the gene editing tool CRISPR to simultaneously increase or decrease expression of four schizophrenia-implicated genes known to harbor eQTLs. The genes were selected because they were deemed most likely to confer disease risk by regulating gene expression. To trigger changes in the direction predicted to heighten risk for schizophrenia, expression was increased for three of the genes and decreased for one.

Manipulating expression of the four genes altered expression of 1,261 other genes 665 increased and 596 decreased. This was many more than would be expected if the genes had been merely acting individually, suggesting an underlying mechanism that is synergistic rather than additive.

This unexpected synergy between gene variants demonstrated how even subtle genetic variations can impact neuronal function, said Brennand. These interactions emphasize the importance of considering the complex nature of schizophrenia and other psychiatric disorders, where a combination of gene variants contributes to disease.

Many of the genes affected downstream contained variants that had been linked to autism spectrum disorder or bipolar disorder, in addition to schizophrenia consistent with other research suggesting genetic overlap across mental disorders.

The experimentally induced gene expression changes mirrored those seen in postmortem brains of people with the three mental illnesses. The same changes were also seen in induced pluripotent stem cell neurons from people with childhood-onset schizophrenia, a rare form of the illness thought to be more genetic in origin.

Notably, all of these gene changes resulted in loss-of-brain-function effects when screened one-at-a-time in a zebrafish model, said Brennand. We have added several of them to a list of genes worthy of further study for possible involvement in schizophrenia. There is an overwhelming need for future studies to similarly model such multi-gene interactions in complex cells and circuits.

GRANTS: MH101454,MH106056,MH109897

About the National Institute of Mental Health (NIMH):The mission of theNIMHis to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit theNIMH website.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

Schrode N, Ho S-M, Yamamuro K, Dobbyn A, Huckins L, Matos MR. Cheng E, Deans PJM, Flaherty E, Barretto N, Topol A, Alganem K, Abadali S, Gregory J, Hoelzli E, Phatnani H, Singh V, Girish D, Aronow B, Mccullumsmith R, Hoffman GE, Stahl EA, Morishita H, Sklar P, Brennand KJ. Synergistic effects of common schizophrenia risk variants. Nature Genetics, September 23, 2019.DOI: 10.1038/s41588-019-0497-5

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Gene regulators work together for oversized impact on schizophrenia risk - National Institutes of Health

New Gene Editing Technique Shown to Correct COL7A1 Gene in RDEB Cells – Epidermolysis Bullosa News

A novel gene editing technique was able to correct mutations inCOL7A1 in cells taken from people with recessive dystrophic epidermolysis bullosa (RDEB), providing a proof of concept for using the editing technique in the disease.

The finding was published in theJournal of Investigative Dermatology in a study titled, Base editor correction of COL7A1 in recessive dystrophic epidermolysis bullosa patient-derived fibroblasts and iPSCs.

The idea behind gene editing is simple: If a disease (such as RDEB) is caused by a mutation in a gene (COL7A1), then changing the genetic code to remove the mutation should functionally cure the disease. Of course, rewriting genetic code in living cells much less in human beings is far from simple.

Most current lab techniques basically involve cutting out the section of DNA that has the mutation, then replacing it with a healthy version. The problem is that there are often small insertions or deletions in the code where the DNA is cut, which isnt desirable.

In the new study, researchers tested a novel editing technique that uses a lab-made protein called an adenine base editor (ABE) to change just one nucleotide (a letter in the DNA code) without the need to cut out a whole chunk of DNA.

The researchers tried using ABE to correct mutations in COL7A1in skin cells taken from two RDEB patients. Broadly, they were successful, correcting the mutation in the DNA in about 24% of the cells; these cells also expressed collagen type VII (C7), the protein encoded by COL7A1.

The researchers then used the corrected skin cells to generate induced pluripotent stem cells (iPSCs, a type of cell that will perpetually divide and that, through chemical cues, can be led to differentiate into many different cell types). These iPSCs still expressed C7, providing a proof of concept that could be helpful in translating these findings into patients.

The researchers also surveyed other spots in the cells genomes to see whether there were any places the ABE was making changes it wasnt intended to. They didnt find any, suggesting a fairly low off-target rate.

Collectively, our study shows the feasibility of autologous cellular engineering using base editing to correct COL7A1 mutations in cell populations currently employed clinically for RDEB, the researchers concluded.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.

Total Posts: 12

Ins Martins holds a BSc in Cell and Molecular Biology from Universidade Nova de Lisboa and is currently finishing her PhD in Biomedical Sciences at Universidade de Lisboa. Her work has been focused on blood vessels and their role in both hematopoiesis and cancer development.

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Vaginitis Therapeutics Market Overview with Detailed Analysis, Competitive lands – News By ReportsGO

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Can Consciousness be Created? – University Observer Online

Scientists have produced mini brains that mimic preterm babies brains, have they created consciousness too? Jade Norton investigates.

It is difficultfor us to comprehend our own consciousness, let alone try to operationallydefine it in a scientific experiment. In the last centuryscientificadvancement has allowed for experiments to be conducted that cross the fieldsof possibility and allow humans to play their hand at creation. However, thereare many ethical considerations that come along with this. For example, whatresponsibilities would suddenly arise if a tissue on a bench could not onlyreact to experimental procedures but had an opinion on them? On the other hand,what if the creation of consciousness in the pursuit of understanding can leadto answers that would not have been answered otherwise? This raises thequestion of whether scientists should aim to create consciousness or is itsomething that should be left to the natural world without human interference?

One recentexperiment undertaken by scientists from the University of California, SanDiego used stem cell technology to create cortical organoids or minibrains that are capable of producing brain signals that mimic that ofpremature babies. The brains do not look like a typical human brain and areinstead a smooth pea-sized blob that is encased in a nutrient-rich medium. Theylack the folding seen in a human brain as they do not contain grey and whitematter but are more of a mass of neural tissue. An induced pluripotent stemcell, which is a cell capable of dividing into any cell in the human body withthe right instructions, was used to create the brain cells. These cells dividedand over the course of 10 months grew from base neuronal cells toneuroepithelium-like structures which are similar to that of human braintissue. These organoids were not capableof complex thought but were created with the idea of using them to studyneurological diseases.

Throughout thedevelopment of the tissue nested oscillatory network dynamics were measured, theseare networks of repetitive electrical activity produced by the human brain inresponse to stimuli.This electrical activity can be found in all livingneurological tissue but does not necessarily show consciousness as there is yetto be an electrical ping signalling life as we currently understand it.

The team in SanDiego measured oscillatory spikes from the minibrains weekly usingmicroelectrode arrays and found an increase in activity as the monthsprogressed. This implied that there was a neural network capable of newdevelopment contained in the tissue. The electrical activity spawned by theneural network of the cortical organoids produced in the lab was recorded andsaved. Then using an EEG (electroencephalograph) the scientists measured the neuralactivity of a premature baby. These neural patterns were compared to see ifthere was a substantial difference between the neural activity between them.The comparison used a subset of features from the EEG to offset variablefactors not found in the cortical organoid. The results of comparison using amachine-learning algorithm found that the development of each tissue had manysimilarities which were likely to have been part of a genetically programmedtimeline. However, these minibrains were unable to progress to furtherdevelopment than that of a premature baby and it is thought that this is due tothe lack of sensory input that would usually be felt through the womb by apremature baby.

The minibrains that were developed in this experiment did not have any evidence ofconsciousness and were almost one million times smaller than a human brain andwithout the multiple types of cerebral cells they didnt have the capability ofdeveloping the full neurological complexity that is needed to form consciousnessas we see it. The measurements of electrical activity were done withoutcomparison of physiological features which varied greatly between the twotissues and have an effect on the maturation of neurons essential fordevelopment. The reality of creating a sentient being similar to ourselves isstill resting in the world of science-fiction, but the ability to create atissue that mimics brain activity and can be used in medical research is adefinite possibility. Brains can now be grown on a petri dish, but as of yetthey havent voiced any complaints.

The ability togrow an organoid that has an extensive neural network that is similar to thatof a preterm baby raises the question of at what point does consciousnessarise? It depends on who you ask. The origin of consciousness has yet to have auniversal consensus and without it there are no clear ethical rules relating tothe growth and development of cerebral tissue. There is no indicator that willtell you that consciousness has been created so it is possible that there is oronce was a homegrown sentient lab tissue somewhere.

Along with theadvancements in organoid technology, ethical considerations will continue tocome into question. Without the ability to know when consciousness has dawned,how do you know if the organoid is feeling pain or is distressed? And oncesomething develops a consciousness it becomes a subject of an experiment ratherthan an object which entitles it to its own rights. Consequently, this wouldseem that it would give scientists the responsibility to uphold these rights,however, this is still a largely unexplored area.

With theknowledge of ethical responsibility in hand, the possibilities of opportunityfor advancement is huge with a literal minibrain to work with. Medical researchcan use these organoids to see the in vivo effects of certain mental illnessessuch as schizophrenia and epilepsy and see the progression of neurodegenerativediseases such as Parkinsons and Alzheimers without the invasive problem ofviewing it in a live person. The question of when consciousness begins issomething that can fuel a philosophers career but for a scientist the creationof consciousness is a possibility that has never before been so accessible,with increasing advancements we may soon have our own brain in a jar.

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Can Consciousness be Created? - University Observer Online