I-Corps: Viral vector platform technology for cell type-specific gene delivery

The broader impact/commercial potential of this I-Corps project is the development of a precision gene therapy technology for the treatment of genetic diseases and cancer. Gene therapy is a technique that modifies a person’s genes to treat the cause of the disease, rather than the symptoms. It may offer the possibility to reduce or eliminate the frequent hospitalizations, invasive transplants, and expensive or side-effect-prone therapies that are an everyday reality for current patients.

Viral vectors are a type of gene therapy technology currently used in several therapies that are either approved by the FDA or are undergoing clinical trials. Viral vectors that are safe to use in humans have several limitations including the types of diseases they may treat, high cost, and months-long hospital stays for patients. The proposed technology may address these limitations and represents a significant step towards creating cost-effective and adaptable therapeutics for patients with genetic disorders and cancer.

This I-Corps project is based on the development of user-configurable, viral vector platform technology for cell type-specific gene delivery for gene therapy applications. The platform uses a genetically engineered Adeno-Associated Virus (AAV) that has been modified to remove its ability to cause infectious disease and to carry therapeutic genes into human cells.

In addition, this AAV has been engineered to allow the attachment of antibodies that direct AAV infection towards cell types and tissues that express the receptor recognized by the antibody. Using the proposed technology, it is possible to target different tissues by “arming” a pre-made, non-infective AAV with a different antibody. Pilot studies using the same batch of pre-made AAV with four different purchased antibodies showed the ability to selectively transduce cells expressing different surface receptors.

Composite AAVs structurally separate precision delivery and therapeutic payload, allowing each to be engineered independently. Furthermore, antibodies have emerged as an approved class of therapeutic agents to numerous human diseases including cancer, auto-immune diseases, and diseases with a hematopoietic origin. Leveraging existing antibodies for precise targeting of gene delivery may represent a new mode of action for these drugs, further driving the impact of the proposed technology.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.