Sangamo is developing state of the art AAV-based gene therapies for the treatment of monogenic diseases, such as hemophilia A and certain inherited metabolic disorders.
A gene is a unit of genetic information contained in an organism’s genome or DNA, which encodes the instructions for making a protein. Collectively, genes provide the information for the organism’s development and characteristics. Humans have about 20,000 genes on their 23 pairs of chromosomes.
In monogenic diseases an essential protein isn’t made properly, or in sufficient quantities, as a result of a mutation in a single gene. One therapeutic solution is to deliver a new copy of the defective gene to cells so that they can now make the protein and alleviate symptoms of the disease. This is known as gene therapy.
The new therapeutic gene can be delivered using an engineered virus. As part of their life-cycle, viruses need to deliver their genetic instructions to a cell in order to reprogram it to produce more viral copies. In gene therapy, we can use a harmless virus which has been engineered to deliver the genetic information necessary to make a human therapeutic protein rather than viral proteins. One virus that is commonly used in gene therapy is adeno-associated virus or AAV.
AAV is a naturally occurring virus that infects humans but is not known to cause disease. Engineered AAV has been used as a delivery method for gene therapy in many clinical trials in the U.S. and Europe and has been found thus far to be generally well-tolerated without major side effects.
A gene encoding a therapeutic protein can be packaged into AAV and delivered to cells in tissues such as the liver, the eye, the brain or the heart. Once inside the cell, the gene is unpacked from the virus coat, or capsid, and can then enable that cell to make the therapeutic protein. AAV can be manufactured at a large enough scale for use as a human therapeutic.