Fitting Big Genes into Small Vectors

Many disease‑causing genes are too large to be packaged into standard AAV gene therapy vectors, leaving a long list of otherwise gene-therapy-ready conditions without viable treatments. SpliceBio is leveraging a protein splicing platform based on engineered split inteins to overcome the cargo limitations of AAV gene therapy vectors, enabling delivery of large genes to potentially treat a broad range of monogenic conditions. The company’s lead program is a dual AAV gene replacement therapy to treat Stargardt disease, a rare inherited condition that causes progressive vision loss. Miquel Vila-Perello, CEO of SpliceBio, discusses the company’s platform technology that enables the delivery of large genes in AAV vectors, its work to date in Stargardt disease, and preclinical data across more than 20 large-gene targets supporting its platforms use in ophthalmology and CNS indications.