Church Lab Start-Up Opportunities - October, 2018

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TFome - Any human cell type
Parastoo Khoshakhlagh & Alex Ng
TFome is developing transcription factor driven cell differentiation technology to enable a wide array of cell therapy applications. A synthetic biology based technology platform programs human induced pluripotent stem cells into potentially any differentiated cell type with high efficiency and speed (up to 90% in 4 days). TFome can produce functional neurons, oligodendrocytes, astrocytes, vascular endothelial cells, stromal cells and many other cell types to produce cell therapy products ready for implantation, including oligodendrocyte progenitors for the treatment of Multiple Sclerosis.

Ally Therapeutics - Intrinsically Less Immunogenic Gene Therapies
Tina Liu & Kai Chan
Ally Therapeutics is developing a new technology that enables broader use of AAV gene therapies. The technology improves both safety and efficacy of gene therapy, specifically by reducing innate immune responses against the DNA. Experimental work has demonstrated that by reducing the early innate immune response against AAV, this technology can profoundly reduce downstream cytotoxic T cell responses/toxicity and increase gene expression (by up to 10x), thus widening the historically narrow therapeutic window of gene therapies. This technology has been validated both in vitro (in primary human cells) and in vivo (in mice, pigs, and soon non-human primates). Ally anticipates commercializing this powerful platform technology through developing uniquely enabled gene therapy products and partnering with Biopharma partners.

Tenza - Symbiotic drug-delivery technology
Anik Debnath
Tenza is developing a novel symbiotic drug-delivery platform employing engineered lactic acid bacteria. Living bacteria from the human microbiome are reprogramed to produce and deliver therapeutic proteins using a proprietary, machine learning-powered genetic bioengineering platform. Such engineered microbes offer a more targeted alternative to conventional drug delivery methods by restricting exposure to the target tissues naturally inhabited by the symbiotic microbe, thereby increasing therapeutic efficacy while reducing systemic side effects. Tenza is currently pursuing animal evaluation of two engineered organisms adapted to the gastrointestinal tract and female genital tract that deliver anti-inflammatory and anti-viral therapeutics for IBD therapy and HIV prevention, respectively.

Gene Delivery via Skin
Denitsa Milanova
Genetic engineering of skin cells poses an entirely new paradigm to gene and immune therapies as it bypasses the natural immune response and forces in vivo translation, production and passive secretion of proteins and antibodies locally or directly to the blood stream across the dermal vasculature. Denitsa's technology is a two-step gene transfer to skin without a requirement for ex vivo genetic engineering. To deliver the therapy, a patch of skin is first treated with cavitational ultrasound, followed by topical application of a formulation of viral particles. Denitsa has created a cutting-edge gene delivery platform broadly applicable to circulating antibody therapies, locally manifesting genetic diseases of the skin, auto-immune diseases, and cosmetic treatment of skin aging. Current preclinical efforts focus on collagen modulation in skin and HIV vaccines, while two additional products are in the pipeline – a rare genetic skin disease and an autoimmune disease of the skin.

Kern Systems - Securing digital data in DNA
Henry Lee
DNA has garnered considerable interest as a medium for digital information storage due to its superior density (1000x) and durability (300x) over existing silicon-based storage media. Additionally, DNA has no foreseeable technical competitor, making it the most compelling medium for storing the world's vast and exponentially growing volume of digital data. Despite these promising advantages, DNA information storage has not been widely adopted due to the prohibitive cost of synthesizing this polymer. Kern Systems is pioneering new approaches for synthesizing DNA using enzymatic methods which are simpler, faster, and importantly, projected to reduce the cost of DNA synthesis by several orders of magnitude. At this scale, the cost of DNA will be competitive with the current price of magnetic tape storage enabling broad market adoption. Kern Systems is positioning itself as the partner of choice for highly secure, long term, cold storage of digital information.

Dyno Therapeutics - AAV Capsid engineering
Eric Kelsic
Enthusiasm for gene therapies to treat chronic life-threatening and debilitating diseases is surging due to recent FDA approvals, clinical successes, and preclinical proof-of-concept for the development of the CRISPR/Cas9 system. However, the major obstacle for successful gene-therapy treatment remains the challenge of achieving efficient delivery of therapeutic DNA in vivo. The Adeno-Associated Virus (AAV) capsid is now the predominant method for in vivo delivery but is limited by the preference of natural virus capsids for off-target tissues and by neutralization via the immune system. Dyno Therapeutics is engineering the next generation of AAV capsids to enhance delivery, tissue specificity, and immune evasion for improved clinical efficacy. Dyno is dramatically accelerating directed evolution of AAV capsids in animal models using a combination of DNA synthesis, next generation DNA sequencing, and machine learning. Novel methods allow the function of hundreds of thousands of different capsids to be tested across multiple tissues and assays in parallel to optimize capsids for clinical delivery. Dyno Therapeutics will partner its stable of tissue-targeted AAV capsids with Biopharma partners to access diverse therapeutic opportunities.

Updated 1-Nov-02018 by GMC. tRNA