The mechanism of how simple gene therapy vectors enter cells, The research team identified a new cellular input factor for the type of adeno-related virus (AAV), the virus vector most commonly used for gene therapy in vivo.
AAVs are vectors or vehicles produced by viruses that have been made harmless by molecular engineering and which have been shown to promise the transportation of gene therapy treatments to the tissues involved and now the mechanism of how simple gene therapy vectors enter cells.
The researchers found that GPR108, a protein-coupled receptor, functions as a molecular “key” in cells. GPR108 is required for most AAVs, including those used in gene therapy that are approved for cell access.
Because access to cells is an important step in providing gene therapy, these findings can provide important information that will one day enable scientists to better explain, predict, and ultimately send AAV genes to certain tissues.
This finding could enable scientists to better control the transfer of AAV genes to target cell tissue for the treatment of certain genetic disorders.
Gene therapy emerged as an area about 50 years ago, but only in the last decade have scientists made progress in sending genetic material to target cells by AAV.
Despite recent advances in AAV research, scientists are limited in the ability to develop and test additional therapies because its mechanism of action is unclear.
Each band is the cellular factor on which AAV is based and ultimately makes it the core. Remarkably, the Stanford researchers identified an important block in the highly conserved AAVR receptor called AAVR a few years ago.
In this study, the researchers examined 100,000 genes by a screening tool for the entire genome and determine which cells play a role in the fight against AAV. They identified GPR108 as a very eternal entry factor needed to introduce all AAV variants tested with the very different AAV5 exceptions.
GPR108 has proven to be very important for most AAVs currently undergoing clinical testing, including AAV used in both FDA-approved gene therapies.
This finding has been found both in in vitro and in vivo mouse models and provides a mechanical understanding to explain and predict how AAV gene therapy targets tissues and cells.
Our study highlights the mechanistic role of GPR108 in AAV entries. With this knowledge, scientists can further enhance their understanding of the safety of AAV gene therapy, gene targeting and other traits of this new class of agents, the researchers said. The team plans to further investigate this mechanism and AAV biology to optimize these vectors for therapy. His team is working on developing vectors that target certain genetic eye diseases such as retinitis pigmentosa and Usher’s syndrome.
Gene therapy for eye disease is the main focus of our Massachusetts Eye and Ear Research Mission, where our goal is to eliminate blindness.