Rescue Hearing’s initial gene therapy product will target a genetic mutation known to cause progressive hearing loss which eventually leads to deafness.
What is a gene? 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.
What is gene therapy? 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.
What is a viral vector? The new therapeutic gene can be delivered using an engineered virus called a viral vector. 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 vector 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.
Components of a Viral Vector2
Gene Cassette: small piece of DNA containing the therapeutic gene
Capsid (protein shell): directs therapeutic gene to target cells (e.g. hair cells)
AAV Viral Vector: Capsid + Gene Cassette = AAV viral vector
Delivering the new gene2
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 ear. 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.
1. Gene Therapy. http://www.sangamo.com/technology/gene-therapy. Accessed June 2017
2. Gene Therapy Information (PDF). http://www.uniqure.com/gene-therapy/uniqure-technology.php. Accessed June 2017