STTR Phase I: GEX: an mRNA-based tolerogenic vaccine for viral-based gene therapies

The broader impact of this Small Business Technology Transfer (STTR) Phase I project is to develop a scalable, relatively affordable, easily programmable and specific solution to the problem of unwanted immune response in cell and gene therapies, autoimmunity, and transplantation. If successful, this could greatly expand the number of patients who are able to be treated by these types of therapies, including many suffering from rare diseases with little or no current treatment options. The proposed project uses mRNA technology and novel anti-adjuvant technologies, to train the immune response to ignore an antigen encoded in the delivered mRNAs. This project focuses on adeno associated virus-based gene therapies, but the insight gained can be applied in other conditions when hyperactive immune response against self or foreign antigens creates unwanted result. Current gene therapies face a number of challenges associated with immune response to delivery vehicles or the therapeutic proteins. Achieving high and persistent level of therapeutic product expression has been a challenge, often leading to failure of therapies and necessitating redosing. The proposed mRNA based tolerogenic vaccine, will prepare the body to receive multiple doses of gene therapies and to achieve higher level of transgenes in light of body’s response to gene therapies. 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.