ViGeneron's REVeRT Technology Found Efficient for AAV Delivery of Large Genes

ViGeneron announced a peer-reviewed publication in Nature Communications that highlights the potential of their proprietary dual adeno-associated virus (AAV) vector technology called REVeRT (REconstitution Via mRNA Trans-splicing).

The data presented in the publication illustrate the successful delivery of genes larger than the typical AAV packaging size, with exceptional reconstitution efficiency. This achievement empowers gene supplementation and the concurrent manipulation of gene knockout and transcriptional activation for various genes.

In today's landscape of gene therapies, therapeutic AAV vectors represent the most effective and widely utilized method. However, ViGeneron notes that their genome packaging capacity, limited to less than 5kb, hinders the vectors' application for expressing larger therapeutically relevant genes, presenting a significant challenge in the realm of novel gene therapies. To address this limitation, ViGeneron has introduced REVeRT, an innovative and versatile approach based on dual AAV vectors. This approach involves dividing genes into two segments and housing them within individual AAV vectors, subsequently facilitating reconstitution through mRNA trans-splicing.

The Nature Communications paper reports that REVeRT has undergone validation both in vitro and in vivo, proving its effectiveness in reconstituting genes and gene editing modules larger than 5kb, which are pertinent to diseases. This technology ensures high levels of gene expression without the production of unintended proteins, thereby reducing concerns related to potential immunogenicity. Furthermore, REVeRT offers flexibility in selecting the split site and can make use of different AAV serotypes via various routes of administration, demonstrating efficient delivery to diverse tissues and organs, including the eye, heart, and brain.

In a mouse model of Stargardt disease, the researchers additionally showcased substantial ABCA4 gene expression, a gene frequently associated with this hereditary retinal condition. Initial experimental data provided support for a potential enhancement of retinal function.

“The data published in this peer-reviewed paper underscore the transformative potential of our REVeRT technology in efficiently delivering large genes," Dr. Caroline Man Xu, Co-founder and CEO of ViGeneron, said in a company news release. "We are making significant progress with the REVeRT approach in our Stargardt program VG801, which is slated to enter clinical trials next year, alongside VG901 for retinitis pigmentosa. This reaffirms our dedication to advancing cutting-edge gene therapies with the potential to transform patients' lives.”

“The REVeRT platform equips us to tackle some of the most prevalent inherited diseases, often linked to large genes. It also enables transactivation, a CRISPR-driven technology that has the potential to modulate multiple genes of any size in both genetic and non-hereditary diseases," said Dr. Markus Kalousek, CBO of ViGeneron. "We are actively exploring strategic partnerships in various disease areas to accelerate the delivery of these transformative treatments to patients.”