Challenges Posed by Immune Responses to AAV Vectors: Addressing Root Causes

Innate Immune Responses to AAV Vectors

Gene replacement therapy by in vivo delivery of adeno-associated virus (AAV) is attractive as a potential treatment for a variety of genetic disorders. However, while AAV has been used successfully in many models, other experiments in clinical trials and in animal models have been hampered by undesired responses from the immune system. Recent studies of AAV immunology have focused on the elimin...

Immune responses to AAV vectors: overcoming barriers to successful gene therapy.

Gene therapy products for the treatment of genetic diseases are currently in clinical trials, and one of these, an adeno-associated viral (AAV) product, has recently been licensed. AAV vectors have achieved positive results in a number of clinical and preclinical settings, including hematologic disorders such as the hemophilias, Gaucher disease, hemochromatosis, and the porphyrias. Because AAV ...

Immune Responses to AAV-Vectors, the Glybera Example from Bench to Bedside

Alipogene tiparvovec (Glybera(®)) is an adeno-associated virus serotype 1 (AAV1)-based gene therapy that has been developed for the treatment of patients with lipoprotein lipase (LPL) deficiency. Alipogene tiparvovec contains the human LPL naturally occurring gene variant LPL(S447X) in a non-replicating viral vector based on AAV1. Such virus-derived vectors administered to humans elicit immune ...

Addressing the Geotechnical Challenges Posed by Soft Clays

Pre-Clinical Assessment of Immune Responses to Adeno-Associated Virus (AAV) Vectors

Transitioning to human trials from pre-clinical models resulted in the emergence of inhibitory AAV vector immune responses which has become a hurdle for sustained correction. Early animal studies did not predict the full range of host immunity to the AAV vector in human studies. While pre-existing antibody titers against AAV vectors has been a lingering concern, cytotoxic T-cell (CTL) responses...