How Viral Gene Therapy Evades the Immune System

Authors

Aayan Ahmed · Ayriya Dadpour · George Chan · Louise Roberts · Oliver Wang

Abstract

Gene therapy is a form of medical treatment aimed to treat or prevent disease by altering a patient's genome. This includes replacing a faulty gene, inhibiting the expression of a pathogenic gene or adding a new gene to the patient's genome. Viral gene therapy is a promising treatment of a range of genetic disorders. However, its clinical efficacy is limited by the host immune responses against viral vectors. Effective immune evasion is hence an important consideration in the development and delivery of viral gene therapies. This poster explores three strategies used to overcome immune mediated barriers: exploiting immune privileged sites, modifying viral capsids to reduce immune recognition, and employing immunosuppression to modulate host immune responses. These approaches have been considered in relation to three disorders for which viral gene therapy has significant therapeutic potential: Leber congenital amaurosis (LCA) which is an inherited retinal dystrophy leading to early blindness in infancy, Duchenne muscular dystrophy (DMD) which causes early onset muscle wasting, and haemophilia A which is a deficiency in clotting factor VIII leading to excessive bleeding even from small wounds. This poster highlights the importance of tailoring the design of the vector and treatment approaches to both the target tissue and the patient's immune response to help minimise the risk of immune destruction of the vector. Understanding and overcoming these immunological barriers will hopefully improve safety, efficacy and delivery of viral gene therapies and support their broader clinical application in the future.

Keywords: gene therapy, adeno-associated virus (AAV), immune evasion, Leber congenital amaurosis, Duchenne muscular dystrophy, haemophilia A

Contact the Authors

Aayan Ahmed — ahmedaayan270@gmail.com

Ayriya Dadpour — ayriya1385@gmail.com

George Chan — georgechan1314@gmail.com

Louise Roberts — louiseroberts162@gmail.com

Oliver Wang — gexer987@gmail.com