Category Archives: Gene therapy

Washington: The research is published in Science Advances.

The gene, called TSC2, codes for tuberin, a protein that acts to inhibit cell growth and proliferation. When mutations occur in TSC2, resulting in a lack of tuberin in cells, the cells enlarge and multiply, leading to the formation of tumors.

To restore the function of TSC2 and tuberin in a mouse model of tuberous sclerosis complex, researchers developed a form of gene therapy using an adeno-associated virus vector carrying the DNA that codes for a condensed form of tuberin (which fits within the vector's carrying capacity) and functions like the normal full-length tuberin protein.

Mice with tuberous sclerosis complex had a shortened life span of about 58 days on average, and they showed signs of brain abnormalities consistent with those that are often seen in patients with the disease.

When the mice were injected intravenously with the gene therapy treatment, however, their average survival was extended to 462 days, and their brains showed reduced signs of damage.

"Current treatments for tuberous sclerosis complex include surgery and/or lifelong treatment with drugs that cause immune suppression and potentially compromise early brain development. Therefore, there is a clear need to identify other therapeutic approaches for this disease," said co-lead author Shilpa Prabhakar, an investigator in the MGH departments of Neurology and Radiology.

"Adeno-associated virus vectors have been used widely in clinical trials for many hereditary diseases with little to no toxicity, long-term action in nondividing cells, and improvement in symptoms," adds Prabhakar.

She notes that benefits can be seen after a single injection, and some forms of the viral vector can efficiently enter the brain and peripheral organs after intravenous injection.

The US Food and Drug Administration has approved a limited number of gene therapy products for use in humans, and the results from this study suggest that clinical trials are warranted to test the strategy's potential in patients with tuberous sclerosis complex.

Go here to see the original:
Gene Therapy Strategy Found Effective in Mouse Model of Hereditary Disease TSC - DTNEXT

BOSTON and LONDON, Jan. 14, 2021 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to OTL-200, an investigationalex vivoautologous hematopoietic stem cell (HSC) gene therapy for the treatment of early-onset metachromatic leukodystrophy (MLD). In late 2020, the FDA cleared the companys Investigational New Drug (IND) application for OTL-200, and the therapy also recently was approved in the European Union (EU) under the brand name, LibmeldyTM.

Receipt of RMAT designation for OTL-200 underscores both the severe nature of MLD and the transformative potential of the therapy for young patients suffering from this devastating, fatal neurodegenerative condition, said Bobby Gaspar, M.D., Ph.D., chief executive officer,Orchard Therapeutics. Alongside our open IND, RMAT designation provides an opportunity for enhanced interactions with the FDA to determine the optimal path to submit a Biologics License Application (BLA) for OTL-200 in the U.S.

Established under the 21st Century Cures Act, the RMAT designation program was created to expedite the development and review of regenerative medicine therapies intended to treat, modify, reverse or cure a serious condition.The FDA granted Orchard RMAT designation for OTL-200 based on data submitted on 39 patients, including 9 patients from theU.S., who have received OTL-200 as part of clinical studies and compassionate use programs conducted at theSan Raffaele-Telethon Institute for Gene Therapy (SR-Tiget)inMilan, Italy. This data set includes post-treatment follow-up data of up to eight years in the earliest treated patients in these programs.

We look forward to continued engagement with the FDA in the coming months to discuss the comprehensive data set we have already collected in the OTL-200 clinical development program and agree on the potential next steps on the regulatory path to approval for this innovative gene therapy, said Anne Dupraz, chief regulatory officer at Orchard.

About Libmeldy / OTL-200

Libmeldy (autologous CD34+ cell enriched population that contains hematopoietic stem and progenitor cells (HSPC) transduced ex vivo using a lentiviral vector encoding the human arylsulfatase-A (ARSA) gene), also known as OTL-200, has been approved by the European Commission for the treatment of MLD in eligible early-onset patients characterized by biallelic mutations in the ARSA gene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. Libmeldy is the first therapy approved for eligible patients with early-onset MLD.

The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies. In addition to the risks associated with the gene therapy, treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability.

For more information about Libmeldy, please see the Summary of Product Characteristics (SmPC) available on the European Medicines Agency (EMA) website.

Libmeldy is not approved outside of the European Union, UK, Iceland, Liechtenstein, and Norway. OTL-200 is an investigational therapy in the U.S.

Libmeldy was developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy.

About Orchard

Orchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and theSan Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard

Investors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (Twitter andLinkedIn), including but not limited to investor presentations and investor fact sheets,U.S. Securities and Exchange Commissionfilings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Forward-Looking Statements

This press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include express or implied statements relating to, among other things, Orchards business strategy and goals, the therapeutic potential of Libmeldy (OTL-200), the likelihood that data from clinical trials will support further clinical development and regulatory approval of OTL-200, and the outcome of planned FDA interactions regarding the potential approval pathway for OTL-200. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation: the risk that prior results, such as signals of safety, activity or durability of effect, observed from clinical trials of Libmeldy will not continue or be repeated in our ongoing or planned clinical trials of OTL-200, will be insufficient to support regulatory submissions or marketing approval in the US or to maintain marketing approval in the EU, or that long-term adverse safety findings may be discovered; the risk that OTL-200 or any one or more of Orchards product candidates will not be approved, successfully developed or commercialized; the risk of cessation or delay of any of Orchards ongoing or planned clinical trials; the risk that Orchard may not successfully recruit or enroll a sufficient number of patients for its clinical trials; the delay of any of Orchards regulatory submissions; the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates or the receipt of restricted marketing approvals; the inability or risk of delays in Orchards ability to commercialize OTL-200, if approved, or Libmeldy in the EU; the risk that the market opportunity for Libmeldy, or any of Orchards product candidates, may be lower than estimated; and the severity of the impact of the COVID-19 pandemic on Orchards business, including on clinical development, its supply chain and commercial programs. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards quarterly report on Form 10-Q for the quarter endedSeptember 30, 2020, as filed with theU.S. Securities and Exchange Commission(SEC), as well as subsequent filings and reports filed with theSEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Contacts

InvestorsRenee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

MediaChristine HarrisonVice President, Corporate Affairs+1 202-415-0137media@orchard-tx.com

View original post here:
Orchard Therapeutics Announces OTL-200 Granted Regenerative Medicine Advanced Therapy (RMAT) Designation by FDA for the Treatment of Metachromatic...

Sana Biotechnology is following the Moderna playbook to a tee: Promise a lot based on very early science, be vague, nab a major VC raise, then gun for an IPO.

While Moderna has, in some respects, come up good after its monster $600 million-plus IPO a few years back and it now looking to literally save the world and the economy with its mRNA vaccine, Sana is looking for a $150 million IPO for its range of preclinical stem cell and gene control platforms.

That $150 million could, if history repeats itself, swell to be much more than that: It raised a gigantic $700 million last summer from a whos who of VCs including Arch Venture Partners, Flagship Pioneering, the Canada Pension Plan Investment Board, Baillie Gifford, F-Prime Capital, the Alaska Permanent Fund, the Public Sector Pension Investment Board, Bezos Expeditions, GV, Omega Funds, Altitude Life Science Ventures and multiple unnamed institutional investors.

Many other early-stage biotech have also lowballed their IPO target only to see it eventually grow to 50% or 100% more than that.

RELATED: In the face of COVID-19, cell and gene therapy space shows 'remarkable resilience': report

Last year, Sana licensed technology from Harvard University to further its efforts to develop off-the-shelf cell therapies, its main pipeline focus. The goal is to genetically modify and differentiate stem cells to create cell therapies that are cloaked from the immune system.

Using this, Sana said at the time it plans to harness these resources to create off-the-shelf cell therapies capable of treating a range of diseases. To achieve that goal, Sana will need to find ways to stop the immune system from rejecting the cells as foreign.

The biotech, run by a bunch of former Juno execs, is focused on a series of disease areas including oncology, diabetes, central nervous system disorders, cardiovascular diseases and genetic disorders.

All of its candidates are, however, in preclinical development, with IND submissions for clinical work not expected until 2022 and 2023, according to its Securities and Exchange Commission filing.

Our vision is to build the pre-eminent company focused on engineered cells to create medicines for patients, it said in its filing. Our mission is to do so at a scale that allows broad accessibility for patients so that we can democratize access to curative therapies.

To achieve this, we have strategically focused on the key limitations for generating engineered cell therapies, whether the cell modulation occurs in vivo or ex vivo. We also continue to aggregate the people and technologies that will allow us to research, develop, manufacture, and ultimately commercialize differentiated products across a range of diseases.

It plans to list as "SANA" on the Nasdaq.

More:
Secretive Sana, still a year away from the clinic, files for an IPO after a mammoth raise - FierceBiotech

Gene therapy pioneer Jim Wilson and the University of Pennsylvania are teaming up with Regeneron to help deliver its COVID-19 antibody cocktail using adeno-associated virus (AAV) tech in the hope of curbing infection via a nasal spray.

The antibody cocktail, made up of casirivimab and imdevimab, was given a speedy authorization by the FDA less than two weeks ago as a treatment for certain COVID-19 patients. But, keeping up with the fast pace of SARS-CoV-02 R&D, Regeneron is not resting on its laurels and now wants to find a quicker way of delivering its therapy while also working on it as a prophylactic.

Accelerate Biologics, Gene and Cell Therapy Product Development partnering with GenScript ProBio

GenScript ProBio is the bio-pharmaceutical CDMO segment of the worlds leading biotech company GenScript, proactively providing end-to-end service from drug discovery to commercialization with professional solutions and efficient processes to accelerate drug development for customers.

RELATED: Regeneron, following in Lilly's footsteps, wins FDA emergency nod for COVID-19 antibody cocktail

These antibodies are currently injected into patients, but Regeneron and Penn will use Wilsons gene therapy know-how to attempt a nasal spray formulation using AAV vectors. The belief is that this could prevent infection with the virus using a technology typically used in high-tech gene therapies.

The group plans to study the safety and effectiveness of using AAV vectors to introduce the sequence of the cocktails virus-neutralizing antibodies directly to nasal epithelial cells and see whether it can help protect against the disease.

The first step is to finish preclinical trials; if successful, an IND will be sent off to the FDA for human trials.

Wilsons team said it was hopeful that introducing the therapy via single dose of AAV will be able to produce similar protection Regeneron has seen for its cocktail, but for potentially a longer duration.

Regeneron scientists specifically selected casirivimab and imdevimab to block infectivity of SARS-CoV-2, the virus that causes COVID-19, and we have been encouraged by the promising clinical data thus far, said Christos Kyratsous, Ph.D., vice president of research, infectious diseases and viral vector technologies at Regeneron.

In the quest to use cutting-edge science to help end this disruptive and often very devastating disease, we are excited to explore alternate delivery mechanisms such as AAV that may extend the potential benefits of this investigational therapy to even more people around the world.

Visit link:
Wilson, Penn ink Regeneron pact to use gene therapy tech to deliver COVID-19 antibodies - FierceBiotech

SALT LAKE CITY (Ivanhoe Newswire)

Gene replacement therapy: Its a game-changer when it comes to treating life-threatening illnesses. It can replace disease-causing genes with healthy genes, knock out a gene thats not working right, or add a new gene to the body to help fight disease. To date, the FDA has approved four types of gene therapy including one that was given the OK just in time to save one little boys life.

No doubt about it, Cinch Wight is going to be a cowboy just like his dad.

He loves the dog and the horses and the cows, shared Cinchs dad, Alex Wight.

But it has been a wild ride for this young bronco. A mandatory newborn screening test at birth revealed Cinch had spinal muscular atrophy or SMA.

Cinchs mom, Amber Wight recalled, That was the first time Id ever even heard the term and what it was. And so, it was very scary.

A neuromuscular disorder that can paralyze a baby in the first few weeks of life.

My first thought was, hes never going to be able to ride broncs or anything like that, expressed Alex.

But just one day after Cinch was born, the FDA approved a new gene therapy.

We were pretty excited to get a phone call from the department of health, you know, and have this baby here who we can use this treatment on after its approval, explained Russell Butterfield, MD,pediatric neurologist at University of Utah Health and Intermountain Primary Childrens Hospital.

A critical gene in little Cinch was missing. Pediatric neurologist Russell Butterfield used an infusion to deliver a virus carrying a new copy of the gene into Cinchs nerve cells.

Its like a delivery truck to deliver genes to where you want them to go. What that does do, is it stops the disease right where it is, elaborated Dr. Butterfield.

Just a few years ago, most children born with SMA didnt make it to their second birthday. Now?

The hardest is holding a baby in one hand and holding that drug in the other and really feeling the weight of that. And understanding that how different this childs life will be with his new medicine, expressed Dr. Butterfield.

It took a lot of courage for this family to get this far. Thats why Alex wrote a book for his son. A true story about how real cowboys never give up.

I wanted to let him know that no matter how hard it gets, as long as he keeps going, hell be all right, shared Alex.

Doctors dont know if the one-time infusion will last a lifetime or will have to be repeated and there could be a possible risk of inflammation to the liver that doctors will closely monitor. The gene replacement therapy costs 2.1 million dollars. Insurance paid for most of it, but Alex hopes sales from his childrens book will help pay the rest. You can find the book, A Cowboy and His Horse, at https://www.amazon.com/COWBOY-HIS-HORSE-ALEX-WIGHT/dp/B08CWG46ZX.

Contributors to this news report include Cyndy McGrath, Executive Producer; Marsha Lewis, Field Producer; Rusty Reed, Videographer; Roque Correa, Editor.

See the original post:
A little cowboy saved by groundbreaking gene replacement therapy - Wink News

Researchers based at the Neuroscience Institute at the University of Sheffield in the UK have identified a new genetic risk factor for Motor Neurone Disease (MND) in so-called 'junk DNA'.

The newly discovered genetic changes are present in up to 1% of MND patients.

The research, published in the journal Cell Reports, focused on genetic mutations in non-coding DNA, often known as junk DNA because it does not directly encode protein sequences. Non-coding DNA makes up more than 99% of the human genome, but currently is relatively unexplored.This research also includes new methods for studying mutations in non-coding DNA which could be applied to other diseases.

The authors of the study reported that they determined an existing neuroprotective drug developed at the University of California San Diego (UCSD) called SynCav1 could help MND patients carrying the newly discovered genetic mutation.

An experimental gene therapy for the treatment of neurological disorders such as MND and Alzheimers disease, SynCav1 has been licensed to CavoGene LifeSciences.

MND or Amyotrophic Lateral Sclerosis (ALS), as it is also known, affects motor neurons in the brain and spinal cord that form the connection between the nervous system and muscles to enable movement of the body. The progressive disease affects a patient's ability to walk, talk, use their arms and hands, eat and breathe.

Around 5,000 people in the UK and 30,000 people in the US are currently living with MND, with numbers expected to rise.

High-income countries currently have the highest rates of motor neuron diseases worldwide, and the burden is increasing with the ageing population, shows an analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016.

Dr Jonathan Cooper-Knock, lead author of the study and NIHR clinical lecturer in Neurology at the Neuroscience Institute at the University of Sheffield, said: "Until now scientists have never systematically examined non-coding or junk DNA in relation to the development of MND.

"Not only have we identified a mutation in junk DNA which puts people at risk of developing a certain form of the MND, but we have also found that by targeting the mutated gene with the established neuroprotective drug called SynCav1, it might be possible to halt or potentially prevent the disease progressing in those patients.

"This is a significant breakthrough in terms of genetic risk factors driving personalized medicine for MND patients."

Read the original:
An experimental gene therapy may be effective for MND patients with a newly discovered genetic mutation - BioPharma-Reporter.com

In the oncology world, theres no better hunting ground for cancer R&D execs than Genentech. The biotech franchise at Roche has worked on some of the leading drugs in the field, proven themselves with blockbuster returns, and carries weight for whatever it says and does.

The exodus of R&D talent out of the South San Francisco hub is a testament to their success.

Now one of their top research execs has been raided by a top China biotech player to satisfy not just their need for an oncology R&D chief as they build up their muscle in discovery and drug development, but also add a spotter for new cancer drug deals.

Unlock this story instantly and join 94,300+ biopharma pros reading Endpoints daily and it's free.

SUBSCRIBE SIGN IN

See more here:
Regeneron teams with gene therapy pioneer James Wilson, adapting its Covid-19 antibody cocktail to an AAV-based nasal spray - Endpoints News

Professor Laurence D Hurst explains why understanding the nucleotide mutations in viruses, including SARS-CoV-2, can have significant implications for vaccine design.

With 61 codons specifying 20 amino acids, some can be encoded by more than one codon and it is often presumed that it does not matter which one a gene uses. When I first studied genetics, some books I read taught that mutations between such alternative codons (eg, GGA->GGC, both giving glycine) were called synonymous mutations, while others referred to them as silent mutations. However, are synonymous mutations really silent meaning they are identical in terms of fitness and function? Although they may specify the same amino acid, does that mean they are all the same?

Figure 1: Intronless GFP transgene expression is higher for variants of GFP with higher GC content at synonymous sites5

Perhaps one of the biggest surprises over recent years has been the discovery that versions of the same gene, differing only at synonymous sites, can not only have different properties, but effects that are not modest.1-5 For example, two versions of green fluorescent protein (GFP) differing only at synonymous sites can have orders of magnitude differences in their expression level.4 We similarly recently discovered that for an intronless transgene to express in human cell lines it needs to be GC rich, which can be achieved by altering the synonymous sites,5 as seen in Figure 1. It is no accident, we suggest, that the well-expressed endogenous intronless genes in humans (such as histones) are all GC rich and that our functional retrogenes tend to be richer in GC content than their parental genes.

The realisation that synonymous sites matter has clear relevance to the design of transgenes or other artificial genes, be these for experiments, gene therapy, protein production (eg, in bacteria) or for vaccine design. In the case of vaccines, we might wish to modulate a viral protein to be effectively expressed in human cells to illicit a strong and robust immune response.6 Conversely to the design of attenuated vaccines, we seek to produce a tuned down version of the virus that can function but is weak.7

The challenge is knowing not just which synonymous sites can be altered but knowing how they should be altered. One approach is mass randomisation try many alternatives and see what works.4,8,9 In principle this is fine, but this approach requires many randomisations, which is still technically difficult for long attenuated viruses. An alternative strategy that we have been exploring is to let nature tell us; we can apply tools and ideas from population genetics to better understand what natural selection favours and disfavours and in turn to estimate the strength of selection.

it will be interesting to see if we can learn a lesson from nature as to how to weaken a virus

Estimation of the strength of selection is possible from knowledge of the site frequency spectrum, (ie, how common variants are) from which we can infer the distribution of fitness effects (DFE). If a site is under strong purifying selection, then mutations may occur in the population but these are rapidly eliminated, so variants are always rare. By contrast, if they are selectively neutral, we expect some variants to be quite common. We recently applied this methodology to show that synonymous mutations in human genes that disrupt exonic splice enhancer motifs are often under strong selection and affect many synonymous sites in our genes.10 This has implications for both diagnostics and for transgene design for gene therapy, as we often remove introns in heterologous genes, so freeing up these residues from their role in specifying exons ceases.11

The same DFE methodology cannot easily be applied to viruses, as the methods assume free recombination (ie, we assume one mutation does not impact the fate of others in the same genome). However, other population genetical tools can still be applied. Recently, we examined SARS-CoV-2 and identified the profile of mutations that we see at four-fold degenerate sites.12 From this profile we could estimate what the synonymous site composition would be, assuming that the only forces are mutational biases and neutral evolution (ie, no selection). We observed that in this genome there is a strikingly strong C->U mutation bias and a G->U one. In the raw data this is not so obvious as G and C are quite rare. However, the mutability of the sites per occurrence of the site reveals the underlying patterns.

Figure 2: The rate of mutational flux from one dinucleotide to another in the coding sequence of SARS-CoV-2. The direction of flux is indicated by the indentation of the connecting links: the inner layer represents flux out while the outermost layer represents flux into the node. The frequency of the flux exchange is represented by the width of any given link where it meets the outer axis. Dinucleotide nodes are coloured according to their GC-content. Hence, it is evident that there is high flux away from GC-rich dinucleotides whereas AU-rich dinucleotides are largely conserved.12

With knowledge of the mutational bias we then asked what the equilibrium frequency of the four nucleotides would be using four simultaneous equations. This is the nucleotide content at which for every mutation changing a particular base there is an equal and opposite one creating the same base somewhere else in the genome, ensuring overall unchanged nucleotide content. Given the strong C->U and G->U mutational biases, it is no surprise that the equilibrium content is very U rich (we estimate equilibrium U content should be about 65 percent). However, while the four-fold sites are indeed U rich, they are not that U rich, being closer to 50 percent. A clue as to why the mutation bias is so skewed to generating U comes from analysis of equilibrium UU content: UU residues are predicted to be very common, with CU residues being particularly mutable generating UU (Figure 2) this is expected due to human APOBEC proteins attacking and mutating/editing the virus.13

One probable explanation for this difference between predicted and observed nucleotide content is selection against U content. There may be many U residues appearing in the population, but many are pushed out of the population owing to purification selection, ie, because of the deleterious effects of the mutations. That such selection is happening in the SARS-CoV-2 genome is also clear from the sequence data. We estimate that for every 10 mutations that appear in the sequence databases, another six are lost because of selection prior to genome sequencing. Indeed, UU content is about a quarter of that predicted (Figure 3).

Figure 3: The predicted (under neutral mutational equilibrium) and observed dinucleotide content of SARS-CoV-2. Note the very high predicted levels of UU given the strong mutational flux to UU residues (see Figure 2) and the net underrepresentation in actual sequence.9

This leaves two problems: why is selection operating on SARS-CoV-2 and what can we do with this information? In some cases, we have a good idea as to why: many mutations to U at codon sites generate stop codons. However, we have observed that U destabilises the transcripts and is associated with lower-reported transcript levels;12 a full explanation of the causes of selection on nucleotide content therefore requires manipulation of the sequences.

The second question, what to do with this information, is perhaps more urgent. It has previously been noted that nucleotide content manipulation is a viable means to attenuate viruses.7 Currently there are three groups investigating this route to make a vaccine for SARS-CoV-2: Indian Immunologicals Ltd/Griffith University, Codagenix/Serum Institute of India and Acbadem Labmed Health Services/Mehmet Ali Aydinlar University. In prior attempts, attention has been paid to CpG levels and UpA levels (which we find to be correlated between SARS genes and between different viruses).12 CpGs attract the attention of zinc antiviral protein (ZAP) and UpA attracts an RNAase L. Not surprisingly, some viruses, including SARS-CoV-2, therefore have low levels of both dinucleotide pairs given the levels of the underlying nucleotides.

The challenge is knowing not just which synonymous sites can be altered but knowing how they should be altered

In the past, attenuation strategies have focused on modulating synonymous sites to increase CpG and UpA, making the virus more visible to antiviral proteins.14 We in turn suggest a general strategy to utilise this method and to increase U content as well.12 Given the evidence that selection on the virus is to reduce U content, while our antiviral proteins are mutating it to increase U content, it will be interesting to see if we can learn a lesson from nature as to how to weaken a virus. This is an unusual circumstance in which we predict that we should build in more of the already most common synonymous site nucleotides (U in this case) to degrade the virus. More generally, it is assumed that the most used codons are those that tend to increase the fitness of the organism. In the face of such a severe mutation bias, however, this simpler logic no longer holds.

Laurence D Hurst is Professor of Evolutionary Genetics and Director of the Milner Centre for Evolution at the University of Bath. He is currently also the President of the Genetics Society. He completed his D.Phil in Oxford, after which he won a research fellowship and then moved to Cambridge University as a Royal Society Research Fellow. While on the fellowship he assumed his current Chair at Bath University. In 2015 he was elected a Fellow of the Academy of Medical Sciences and a Fellow of the Royal Society. He is a recipient of the Genetics Society Medal and the Scientific Medal of the Zoological Society of London.

Related topicsDisease research, DNA, Gene Therapy, Genetic analysis, Genomics, Protein, Proteogenomics, Proteomics, Research & Development, RNAs, Vaccine

More here:
Tweaking synonymous sites for gene therapy and vaccines - Drug Target Review

"The need for reproducible, scalable, and economical production of cell and gene therapies is creating a demand for digital bioprocessing technologies," said Nitin Naik, Global Life Sciences Vice President at Frost & Sullivan. "These technologies are critical to realize the true commercial potential of cell and gene therapies in the next two to three years and serve as a conduit to improve market access and control the total cost of therapy."

Naik added: "From a market segment perspective, while the stem cell market is lucrative, the highest growth is expected to be in gene-modified cell therapies, with a pipeline of 269 products,* followed by gene therapies, which account for 182 assets in the pipeline.* Further, although allogeneic stem cell therapies dominate the marketed product catalogs, interest in disease-modifying CAR-T therapies, which are largely autologous, is driving demand for the evolution of manufacturing technologies, models, and capacity expansion investment by CDMOs." (*as of August 2020)

To tap into the growth prospects exposed by the CGT market, companies must focus on:

Supply Chain Optimization and Decentralized Manufacturing to Expand the Contract Cell and Gene Therapy Manufacturing Market, 20202026 is the latest addition to Frost & Sullivan's Healthcare research and analyses available through the Frost & Sullivan Leadership Council, which helps organizations identify a continuous flow of growth opportunities to succeed in an unpredictable future.

About Frost & Sullivan

For six decades, Frost & Sullivan has been world-renowned for its role in helping investors, corporate leaders and governments navigate economic changes and identify disruptive technologies, Mega Trends, new business models and companies to action, resulting in a continuous flow of growth opportunities to drive future success.Contact us: Start the discussion.

Supply Chain Optimization and Decentralized Manufacturing to Expand the Contract Cell and Gene Therapy Manufacturing Market, 20202026

MF98

Contact:Mariana Fernandez Corporate Communications P: +1 210 348 10 12 E: [emailprotected] http://ww2.frost.com

SOURCE Frost & Sullivan

Read more here:
Technological Advancements in Manufacturing Boost the Cell and Gene Therapy Market, Says Frost & Sullivan - PRNewswire

BOTHELL, Wash., Dec. 1, 2020 /PRNewswire/ --BioLife Solutions, Inc. (NASDAQ: BLFS)("BioLife" or the "Company"), a leading developer and supplier of a portfolio of class-defining bioproduction products and services for cell and gene therapies, today announced two new co-investments with innovation accelerator partner Casdin Capital. The first is a re-investment in iVexSol, a vector manufacturing company founded on a proprietary, next-generation, stable lentiviral vector production process. BioLife Solutions invested $1 million and Casdin invested $4 million in a $15.2 million Series A financing round which was led by a third undisclosed strategic investor. BioLife and Casdin also each converted their respective previous $1.1 million debt into equity in this round.

In a new joint investment, BioLife and Casdin also each agreed to invest $1 million in privately held PanTHERA CryoSolutions,a Canadian startup company that is developing next generation cryopreservation solutions incorporating ice recrystallization inhibitor (IRI) intellectual property. Subject to closing conditions, BioLife will execute a development and license agreement with PanTHERA, under which, BioLife will make milestone development payments up to $2 million over the next 24 months in exchange for exclusive, perpetual, worldwide marketing and distribution rights to the technology for use in cell and gene therapy applications.

Mike Rice, BioLife's CEO, remarked, "Drs. Rod Rietze and Michael Greene and the iVexSol team continue to make progress scaling iVexSol's proprietary manufacturing process. iVexSol has the real potential to disrupt the current viral vector manufacturing process which today results in lower yield and high cost, helping to accelerate the development of novel, life-saving cell and gene therapies. We also secured access to PanTHERA's novel and potentially disruptive IRI technology, which may form the basis of a next generation freeze media product line. We've known Drs. Jason Acker and Robert Ben of PanTHERA for many years and respect the rigor of their work."

"Crossing the early stage chasm with next generation technology is particularly difficult in this field." Eli Casdin, Managing Director at Casdin Capital, commented, "It's exciting to see the innovation accelerator build momentum, connecting entrepreneurs with investment capital, operational experience and commercial distribution. We look forward to making more investments in the months and years ahead."

Aby J. Mathew, PhD, Executive Vice President and Chief Scientific Officer at BioLife and Shaun Rodriguez, Director of Life Science Research at Casdin will join the PanTHERA board of directors at closing. Casdin also has a board observer seat at iVexSol.

About iVexSol

iVexSol is a startup vector manufacturing company founded on a proprietary, next-generation, stable lentiviral vector production process that transforms the way these essential gene-delivery vehicles are made. Its technology will greatly reduce the complexity, cost and development time of these critical reagents, thereby accelerating the development and enabling greater access to life-changing cell and gene therapies. For more information visitwww.ivexsol.com.

About PanTHERA CryoSolutions

PanTHERA CryoSolutions is a Canadian corporation that designs and manufactures patented ice recrystallization inhibitors for use in the cryopreservation of cells, tissues and organs. Launched out of a scientific collaboration between Dr. Robert Ben (University of Ottawa) and Dr. Jason Acker (University of Alberta), PanTHERA aims to enhance the cryopreservation process to improve both research tools and clinical therapy products. For more information visit http://www.pantheracryo.com.

About Casdin Capital

Casdin Capital, LLC is an investment firm focused on disruptive businesses. The firm is positioned to capitalize off an underappreciated, disruptive technology shift now unfolding in the life sciences and healthcare industry. Investment opportunities stretch the entire healthcare continuum and into sectors such as agriculture, industrial manufacturing and traditional information technology. For more information please visit http://www.casdincapital.com.

About BioLife Solutions

BioLife Solutions is a leading supplier of class-defining cell and gene therapy bioproduction tools and services. Our tools portfolio includes our proprietaryCryoStorfreeze media and HypoThermosolshipping and storage media, ThawSTARfamily of automated, water-free thawing products, evocold chain management system,Custom Biogenic Systemshigh capacity storage freezers and SciSafe biologic storage services. For more information, please visit http://www.biolifesolutions.com, and follow BioLife on Twitter.

Cautions Regarding Forward Looking Statements

Except for historical information contained herein, this press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, statements about the Company's expectations regarding the success of iVexSol or Panthera products or processes. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements, including risks and uncertainties related to market conditions, and those other factors described in our risk factors set forth in our filings with the Securities and Exchange Commission from time to time, including our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. We undertake no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable law.

Media & Investor RelationsRoderick de GreefChief Financial Officer & Chief Operating Officer(425) 686-6002rdegreef@biolifesolutions.com

Continued here:
BioLife Solutions & Casdin Capital Innovation Accelerator Announce New Investments in Cell & Gene Therapy Bioproduction Tools - goskagit.com