A Much Better Muscle Targeted AAV Gene Therapy

Delivery is the largest challenge in the ongoing development of gene therapy: how to put enough of a vector into the target tissues without sending too much of it elsewhere in the body, particularly the liver, which is where much of every injected substance tends to end up. This is a big issue for systemic administration of gene therapies intended to affect much of the body, given severe side-effect and deaths that have occurred in human trials at high doses of viral vectors. A greater ability to target specific tissues means that a lower dose can be used, and thus off-target effects produced by the vector itself are minimized. The AAV approach noted here is an order of magnitude better than the standard serotypes when it comes to preferentially targeting muscle tissue. That seems to me a big deal, enough to enable systemic delivery of AAV-based therapies at doses far below those at which toxicity and deaths have occurred in human trials. Recombinant adeno-associated viruses (rAAVs) are the most commonly used vehicles for in vivo gene replacement therapy and gene editing in preclinical and clinical studies, yet selective transduction of specific tissues after systemic delivery remains a challenge. Recombinant AAVs generated using naturally occurring capsids are predominantly sequestered in the liver after systemic injection. This sequestration limits the efficiency of transduction in other organs and poses a particular challenge for gene delivery to skeletal muscle. ...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs