Batavia Biosciences’ Post

An exciting new gene delivery platform... ...and the fact that I share my name with the company developing this platform, is purely coincidental 😉 A novel functional gene delivery platform based on a commensal human anellovirus demonstrates transduction in multiple tissue types. Abstract Anelloviridae is a family of non-enveloped viruses with negative-sense, circular, single-stranded deoxyribonucleic acid (ssDNA) genomes that infect vertebrates and are a ubiquitous component of the human virome. Human anelloviruses evade induction of humoral immune responses and appear to be non-pathogenic. These properties, in conjunction with their enormous genomic diversity and wide tissue distribution, make anelloviruses compelling candidates as vectors for next-generation genetic medicines. Here we report the first gene delivery vector system based on a human commensal virus. This Anellovector is based on a virus of the Betatorquevirus genus. Production is enabled by the development of the Self-Amplifying Trans-complementation of a Universal Recombinant aNellovector (SATURN) system, which relies on a self-replicating plasmid to provide viral proteins in trans that drive replication and capsid-dependent packaging of vector genomes. The SATURN system also utilizes a Cre-lox-based recombination mechanism to generate single unit-sized circular genomes inside the MOLT-4 production cell line. We demonstrate that the SATURN system can package a vector genome from a single betatorquevirus with capsids from multiple betatorquevirus species, supporting the feasibility of establishing a novel vector platform that takes advantage of the remarkable diversity of anelloviruses. The Anellovector demonstrated function in vitro in retinal pigment epithelial (RPE) cells. The Anellovector also demonstrated durable in vivo function in the mouse eye for 9 months after subretinal administration, and achieved comparable gene expression to dose-matched adeno-associated virus 9 (AAV9) when transduced by the intracerebroventricular (ICV) route of administration. To our knowledge, this is the first report of a functional anellovirus-based gene therapy vector. Anellovectors have great potential to deliver safe, redosable, and potent therapeutics, helping to expand the reach of programmable medicines. https://lnkd.in/eYNjhFkw

Adeno-associated viral vectors (AAVs) are mainly used in gene therapy to treat genetic disorders caused by a single gene mutation, known as monogenetic disease. However, up to 70% of patients already have antibodies to AAVs, and those who do not are likely to develop antibodies after the first dose. Therefore, #AAV-based gene therapies can only be used once and must be administered in high doses to deliver the gene to a sufficient number of cells, increasing the risk of side effects. Ring Therapeutics' scientists reported that a viral vector developed using their Anellogy platform successfully delivered a gene to the retina of mice. The company's Anellovectors were expressed at stable levels for up to nine months (expression levels comparable to AAV9 vectors) with no signs of toxicity. In this study, the company assessed a vector based on the genus Betatorquevirus. With the new preclinical results in hand, Ring Therapeutics is preparing to initiate investigational new drug studies. The company's work is not limited to mice - during the European Society of Gene and Cell Therapy Annual Congress in October last year, the company announced that it had successfully used an anellovector to deliver a gene to the retina in a pilot study in non-human primates.

What have they been hiding? Passing along an article I read from Dr. Robert Malone’s substack. A summary of is known about the jab, highlights below. #covid 1. The modified mRNA and adenoviral vectored products are not “traditional” vaccines, employ cutting edge gene delivery or gene therapy technologies, and should be regulated as gene therapy products. 2. These “leaky” products did not prevent infection, replication, and spread of SARS-CoV-2, and indiscriminate mass administration of these products contributed to evolution of more antibody-resistant viral strains. 3. In contrast to official HHS communications, these products distribute throughout the body after injection, and are not localized to injection site and associated lymph nodes. This wide distribution contributes to product toxicity and risk, as the body responds to both the genetic delivery particles themselves as well as the encoded proteins which these products cause the body to mount inflammatory responses to the cells and tissues which receive these products. 4. The viral “spike” protein which these products cause patients’ bodies to manufacture is a genetically engineered toxin. 5. The lipid nanoparticle formulation used to deliver the modified mRNA has intrinsic toxicity in humans. 6. These products do not deliver natural messenger RNA, but rather a synthetic chemically modified form with extended stability which cause the body to produce “frameshifted” unnatural, unintended proteins. 7. These products are contaminated with previously undisclosed short DNA fragments which are co-delivered into tissues and cells of patients (together with the modified m-RNA), and which at an unknown and uncharacterized frequency damage patients’ genomes. 8. Analysis of public databases clearly demonstrate a causal relationship between administration the these products and a variety of toxicities including cardiac damages, central and peripheral nervous system damages, damage associated with abnormal blood clotting, and death. 9. Public health data from a wide variety of western government sources demonstrate that the repeated administration of these modified mRNA products are associated with “negative efficacy” (increased risk of COVID disease) beginning between one and three months after administration. https://lnkd.in/g56EKpUP

Very exciting news! We're announcing our latest collaborative breakthrough in Cell & Gene therapies utilizing ProteoNic's 2G UNic™ premium vector technology; we've developed improved lentiviral (LV) vectors that drive up to 5-fold higher functional LV titers! 🧬🔬 Why is this significant? Higher viral titers directly impact overall process efficiency, making therapies more cost-effective and accessible. Our joint efforts address critical challenges in production, capacity, and payload expression, aiming for the ultimate benefit to patients. Frank Pieper, CEO of ProteoNic, says, "We are excited to see our collaboration with Necstgen achieving this important milestone. We will continue our efforts aimed at improving AAV and LV vectors, catering to both transient production systems and stable viral producer cell lines". Paul Bilars, CEO of NecstGen, adds, "These significant results show the strength and importance of our local ecosystem and highlight how collectively we can address the challenges of Cell and Gene Therapy development and their translation to solutions for patients and society." What's next? ProteoNic will offer licensing and co-development opportunities, while NecstGen will integrate the technology into its CDMO activities to make these advancements broadly accessible. Want to learn more? Contact Tristan Pritchard-Meaker for all your enquiries. https://lnkd.in/ezGe3yU3

An interesting read from fierce biotech today.. In the summer of 2020, Tuyen Ong, M.D., was leading Biogen's ophthalmology unit after its acquisition of Nightstar Therapeutics, where he had advanced gene therapy vector development. Initially content with his role, Ong's interest shifted after a conversation with Avak Kahvejian, Ph.D., from Flagship Pioneering, who introduced him to Ring Therapeutics. This company was developing Anellovectors, a new class of viral vectors derived from anelloviruses, which could potentially address the limitations of adeno-associated viruses (AAVs) used in gene therapy. By May 2024, Ring Therapeutics presented promising data at the American Society for Gene and Cell Therapy (ASGCT) meeting. The Anellovectors demonstrated the ability to express genes in primate retinas and could be dosed multiple times without causing toxicity. This advancement overcomes major hurdles associated with AAVs, such as limited tissue penetration and the inability to re-administer treatments due to immune response. Anelloviruses, which are benign and present in most humans, show high tropism and minimal immune rejection, making them ideal for gene therapy vectors. The development of Anellovectors was accelerated by Ring's Anellogy platform, which enabled the team to understand the virus's structure and turn it into a vector more quickly than previous technologies. Ring Therapeutics aims to first apply Anellovectors to treat wet macular degeneration, an eye condition currently managed with regular anti-VEGF protein injections. Anellovectors could provide a more efficient, less inflammatory, and potentially re-dosable alternative, aiming for broader access and better patient outcomes. full article: https://lnkd.in/et9pS67N #biotech #viralvectors #oncology #randd

Viral Vectors and Plasmid Manufacturing – Market expansion driven by a slew of gene therapy approval   Ø A viral vector can be genetically engineered to deliver and insert new genes directly into cells. As viruses are naturally efficient at delivering their own genetic material into host cells for their own replication, they are used as vectors   Ø Adeno-associated virus (AAV) and lentivirus are two most widely used viral vectors in clinical stage. AAV drives adoption in an increasing number of indications and have been evaluated in more than 200 human studies, including the ones that supported Roche’s LUXTURNA and Novartis’ ZOLGENSMA approval offering validation for a favorable clinical profile of the platform   Ø Lentiviruses are a subtype of the Retroviridae family of viruses as they have an RNA genome that is converted to DNA by a virally encoded enzyme called reverse transcriptase. bluebird bio is a leader in lentiviral gene therapy and ZYNTEGLO (LentiGlobin), a lentiviral gene therapy received approval for transfusion-dependent β-thalassemia patients Ø As it is time-consuming to produce large quantities of pure, safe, and potent GMP-grade viral vectors in-house, biopharma companies are also turning to CDMOs to produce their lentivirus and retroviral vectors. Catalent, WuXi Biologics, Lonza, Fujifilm DioSynth, and Thermo Fisher are the leading players facing the third-party CDMO market   Ø Innovation in viral vector manufacturing is crucial as the industry moves from small batches to bigger volumes for larger patient populations. Numerous innovative strategies have also been adopted to modify and improve AAV’s performance such as organ/tissue distribution and transduction efficiency for potential application in expanded indications for larger patient population   Ø Further, innovation in capsid design will create more novel AAVs for therapeutic applications. For example, Dyno is looking to use artificial intelligence to rapidly optimize and develop novel AAV capsids by optimizing targeting ability, payload size, and manufacturability of AAV viral vectors   #genetherapy #cellandgenetherapy #cgt #strategy #marketintelligence #competitiveintelligence #eosintelligence #perspectives #cmo #cdmo #management #consulting #pharmaceuticals  #marketresearch #marketing #leadership #lifesciences #healthcare #precisionmedicine #pipeline #pharmainnovation #marketanalysis #roche #novartis #bluebirdbio ----------------------------------------------------------------------------------- Ready to leverage the power of intelligence to drive "Gene Therapy" product development and commercialization strategy? At EOS Intelligence, we offer competitive intelligence monitoring services in key therapeutic areas to make you stay ahead of the curve. Let us know your perspectives & challenges and we will get you covered. Write us at [email protected]

Complete Guide of " Viral Vector And Plasmid DNA Manufacturing " Download free sample PDF : (https://lnkd.in/dhMKPy2d) The viral vector and plasmid DNA manufacturing market size was valued at USD 6.19 billion in 2023 to grow at a compound annual growth rate (CAGR) exceeding 20.3% from 2023 to 2032. The primary factors driving the market is the advancement in #genetherapy, as the development of new gene therapies is heavily reliant on high-quality viral vectors and plasmid DNA. Furthermore, improvements in manufacturing processes have made it possible to produce viral vectors and plasmid DNA more efficiently at larger scales, while also reducing costs and improving overall quality. Increase in investments in cell and gene therapy research space, there is exceptional demand for viral vectors in the market. Owing to this, various organizations are providing funds to accelerate developments in the manufacturing processes for viral vectors. For instance, in September 2019, Next Generation Manufacturing Canada provided USD 1.89 million to a consortium led by iVexSol Canada. This fund was provided for the development of an advanced manufacturing process for lentiviral vectors. 2iVexSol Canada is a vector manufacturing company that has collaborated with several companies to develop an advanced LVV manufacturing platform. Based on the disease, the cancer segment dominated the market in 2023 with a largest revenue share of 37.85%. According to Globocan, the number of new cancer cases is anticipated to reach 28.4 million within the next two decades, with a rise of 47% from 2020, owing to adoption of western lifestyle, high consumption of alcohol, smoking, poor diet choices, and physical inactivity. Growing number of cancer cases is projected to propel the demand for gene therapies to treat cancer patients, consequently, increasing demand for viral vectors and plasmid DNA for the development of these gene therapies.   North America dominated the market and accounted for 49.11% share in 2023. This can be attributed to the growing engagement of companies in research and product development in gene & cell therapy coupled with a substantial number of contract development organizations in the region. In addition, homegrown companies are expanding their manufacturing facilities in the region.The U.S. held the highest revenue share in North America viral vectors and plasmid DNA manufacturing market owing to the presence of key market players, including CDMOs offering GMP manufacturing services, and the adoption of highly innovative manufacturing technologies for production.

Regeneron Pays Mammoth $100M to Access #CRISPR Enzymes for #AAV Delivery:- •Regeneron is paying $100 million to work with Mammoth Biosciences on delivering in vivo CRISPR-based gene editing therapies to multiple tissues and cell types. •The companies have potentially complementary technologies that could combine to address one of the key barriers to wider use of genetic medicines. Scientists know the genetic causes of many diseases and in CRISPR they have a system for editing DNA to cure patients. However, the vectors typically used to deliver genetic medicines are too small to carry normal CRISPR-Cas systems and can only target the liver. •Mammoth has a potential solution for the capacity problem. Adeno-associated viruses (AAV) vectors can carry genes up to 4.7 kb. Cas9, a widely used CRISPR enzyme, is 4.1 kb. The size makes it impossible to simply pack Cas9 and associated gene-editing machinery into a single AAV vector. •Researchers have come up with a range of potential workarounds. Mammoth’s answer is to use smaller Cas enzymes. Commonly used variants of Cas9 and Cas12 have 1,300 or more amino acids. Mammoth’s NanoCas and CasPhi have around 450 and 750 amino acids, respectively. The size makes it possible to put the enzymes, guide RNA, tissue-specific promoters and other molecules in an AAV vector.