Sub-retinal delivery of closed-ended DNA (ceDNA) using a retina-specific cell-targeted LNP (ctLNP) demonstrated broad photoreceptor distribution, durable expression and tolerability in rodents; potential to address inherited retinal diseases with full gene replacement

Uniform retinal transduction and tolerability also demonstrated for ctLNP delivery of mRNA following sub-retinal injection in non-human primates; potential best-in-class non-viral delivery of mRNA for gene editing in the retina

CAMBRIDGE, MA, USA I October 22, 2021 I Generation Bio Co. (Nasdaq: GBIO), a biotechnology company innovating genetic medicines for people living with rare and prevalent diseases, today presented new preclinical data demonstrating widespread delivery of multiple nucleic acid cargos to photoreceptors using the company’s cell-targeted lipid nanoparticle (ctLNP). The findings were shared in an oral presentation at the European Society of Gene and Cell Therapy (ESGCT) 2021 Annual Virtual Congress.

“We’re excited to extend the benefits of our highly specific, cell-targeted LNP to the retina, where non-viral delivery of nucleic acids has long been held back by poor tolerability and low expression. Our ability to selectively deliver multiple nucleic acid cargos to the retina using ctLNP may allow us to address a variety of inherited retinal diseases using full gene replacement or gene editing,” said Matthew Stanton, Ph.D., chief scientific officer of Generation Bio.  

Sub-retinal delivery of Generation Bio’s proprietary closed-ended DNA (ceDNA) using ctLNP demonstrated broad photoreceptor distribution and durable expression in rodents. Expression was comparable to AAV5 delivery, and ctLNP-ceDNA was well-tolerated without evidence of photoreceptor degeneration, supporting the potential for full gene replacement to address inherited retinal diseases.

Data were also presented for sub-retinal delivery of mRNA using ctLNP, representing the first-ever demonstration of species translation from rodents to non-human primates with tolerability and uniform photoreceptor expression. Distribution with ctLNP was broader and more uniform than that achieved with AAV5 in mice, and total expression was comparable to AAV5. These findings suggest ctLNP as a best-in-class non-viral delivery system for mRNA, potentially enabling gene editing in the retina.

“Diseases such as Stargardt cannot be addressed with traditional viral-based genetic therapies due to the limited cargo capacity of the viral vector. We believe these data using our non-viral genetic medicine platform provide a promising path to treat this challenging disease and others like it, and may expand our platform’s potential to enable multiple therapeutic modalities, including full gene replacement and gene editing,” said Tracy Zimmermann, Ph.D., chief development officer of Generation Bio. “We are excited for the potential for our non-viral delivery technology to expand therapeutic opportunities in the retina as well as to target other tissue types for the treatment of a broad range of diseases.”

To view the digital presentation, please visit Generation Bio’s website.

About Generation Bio
Generation Bio is innovating genetic medicines to provide durable, redosable treatments for people living with rare and prevalent diseases. The company’s non-viral genetic medicine platform incorporates a novel DNA construct called closed-ended DNA, or ceDNA; a unique cell-targeted lipid nanoparticle delivery system, or ctLNP; and a highly scalable capsid-free manufacturing process that uses proprietary cell-free rapid enzymatic synthesis, or RES, to produce ceDNA. The platform is designed to enable multi-year durability from a single dose, to deliver large genetic payloads, including multiple genes, to specific tissues, and to allow titration and redosing to adjust or extend expression levels in each patient. RES has the potential to expand Generation Bio’s manufacturing scale to hundreds of millions of doses to support its mission to extend the reach of genetic medicine to more people, living with more diseases, around the world.

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SOURCE: Generation Bio