Nature Communications publication reveals highly efficient AAV delivery of large genes using ViGeneron´s REVeRT technology

• REVeRT, a dual vector approach based on mRNA trans-splicing, enables delivery of genes larger than the usual AAV packaging size in various tissues

• Potential to address prevalent inherited diseases caused by larger genes such as Stargardt disease
• Delivery of CRISPR modules allows bi-directional modulation of multiple genes

Munich, Germany, October 25, 2023 –– ViGeneron GmbH (ViGeneron), a next-generation gene therapy company, announces a peer-reviewed publication in , showcasing the potential of its proprietary dual adeno-associated virus (AAV) vector technology based on mRNA trans-splicing, REVeRT (REconstitution Via mRNA Trans-splicing). The data demonstrate the delivery of genes larger than the usual AAV packaging size with high reconstitution efficiency, enabling gene supplementation or simultaneous knockout and transcriptional activation of different genes.

While therapeutic AAV vectors are the most efficient and widely used method for gene therapies today, the low genome packaging capacity of < 5kb limits the vectors’ use for the expression of larger therapeutically relevant genes and therefore poses a major challenge for the development of novel gene therapies. REVeRT, an innovative and flexible dual AAV vector-based approach, aims at overcoming this constraint by splitting genes into two parts and packaging them into individual AAV vectors followed by reconstitution via mRNA trans-splicing.

Researchers in today’s Nature Communications paper report that REVeRT was validated both in vitro and in vivo for the efficient reconstitution of disease relevant genes and gene editing modules larger than 5kb. The REVeRT technology achieves high expression levels of selected genes without generating alien proteins as side products, thereby mitigating potential immunogenicity concerns. REVeRT allows flexible selection of the split site and can utilize various AAV serotypes through different routes of administration, demonstrating efficient delivery to various tissues and organs, including eye, heart and brain.

In a mouse model of Stargardt disease, the researchers further demonstrated high expression of ABCA4, a gene frequently involved in this inherited retinal disease. Preliminary experimental data supported a potential improvement of retinal function.

Dr. Caroline Man Xu, Co-founder and CEO of ViGeneron said: “The data published in this peer-reviewed paper underscore the transformative potential of our REVeRT technology in efficiently delivering large genes. 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.”

Dr. Markus Kalousek, CBO of ViGeneron, added: “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. We are actively exploring strategic partnerships in various disease areas to accelerate the delivery of these transformative treatments to patients.”

About ViGeneron GmbH

ViGeneron is dedicated to bringing innovative gene therapy innovations to people in need. The company is advancing its proprietary gene therapy pipeline to treat ophthalmic diseases, while partnering with leading biopharmaceutical players in retinal diseases, CNS, cardiovascular and other disease areas. ViGeneron’s three novel next-generation gene therapy platforms are geared towards addressing the limitations of existing adeno-associated virus (AAV)-based gene therapies. The first, vgAAV vector platform, enables a superior transduction efficiency of target cells and is designed to overcome biological barriers, thus enabling novel, less invasive routes of administration such as intravitreal and systemic administration. The second, the REVeRT (REconstitution Via mRNA Trans-splicing) technology platform, allows efficient reconstitution of large genes (>5kb) in any tissue which can be targeted with a given capsid. The third, AAV Transactivation is a CRISPR-Cas–based AAV gene therapy platform that enables to regulate one or multiple genes in vivo by increasing their expression or by gene knock out. Privately-owned ViGeneron was founded in 2017 by a seasoned team with in-depth experience in AAV vector technology and clinical ophthalmic gene therapy programs and is located in Munich, Germany. For further information, please visit .