Generation Bio Co. presented five posters on its immune-quiet DNA (iqDNA) and cell-targeted lipid nanoparticle (ctLNP) platforms as well as its enzymatic synthesis manufacturing at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting. A sixth presentation on the company's ctLNP platform will be discussed in an oral presentation on May 11, 2024.

Data included in the posters describe iqDNA as a modified, structured, partially single-stranded DNA that evades innate immunity while remaining transcriptionally active in the cell. In mouse studies, the immune profile of iqDNA is consistent with avoidance of key innate immune pathways such as cGAS-STING, which is known to have a significantly lower binding affinity for single-stranded DNA than double-stranded DNA. Given the non-immunogenic nature of iqDNA, Generation Bio believes it can now create novel therapies with a wide therapeutic index, which has been a major challenge to the development of in vivo DNA-based genetic medicines.

The company invented iqDNA using its proprietary rapid enzymatic synthesis (RES) for DNA production. RES is a cell-free process that permits chemical and structural changes with a high degree of control, facilitating heightened DNA functionality through engineering molecular design and components. Because RES does not rely on cellular or viral components, it consistently produces 99% pure material in approximately one week, marking a significant improvement over biologic methods, which are often lengthy and complex.

Further, due to the nature of enzymatic processes, iqDNA can be manufactured at scale to support clinical and global commercial demands without the challenges faced by cell-culture based production. Generation Bio continues to leverage RES to advance its iqDNA platform by optimizing various structural and chemical elements. In new data presented at ASGCT, a second generation of iqDNA achieved higher luciferase expression than first-generation iqDNA.

The company is currently testing formulations of second-generation iqDNA encoding Factor VIII. The company?s ctLNP platform is designed to reach a broad set of target cell types and tissues with exquisite selectivity. Data presented at ASGCT describe the foundation of the platform, Generation Bio?s ?stealth?

LNP, which was engineered in part by making structural modifications to the parental ionizable lipid composition. Cell-specific targeting is achieved by optimizing ligand selection and linker chemistry. Additional data on T cell delivery, including the in vivo delivery of therapeutic transgenes via ctLNP, will be discussed in an oral presentation on May 11, 2024.