Platform for Skin Gene Therapy
A gene therapy startup emerging from the lab of George Church intends to deploy adeno-associated viruses (AAV) for gene transfer in the skin. The nascent company, called MARBLE, aims to target genetic diseases of the skin as well as age-related declines in skin function and appearance, combining classic monogenic disease targets alongside novel aging driver genes.
While AAV has the best safety profile and history of clinical efficacy of any gene therapy vector, it has not previously been applied to skin indications due to a number of technical limits. Transduction of cells in situ within the skin is inefficient, and diffusion within the skin limited. The small packaging capacity of AAV constrains the use of large transgenes, such as structural proteins essential for treating diseases of the skin. More fundamentally, delivery across the outer barrier of the skin is difficult, with established methods being highly variable and mechanically traumatic, resulting in an immune response which complicates future applications using the same AAV system.
A technology platform developed in the Church Lab addresses these issues through a combination of molecular and materials innovations. Researchers have identified multiple AAV serotypes with strong ability to infect skin cells, enabling gene transfer and avoidance of preexisting immunity. The technology enables delivery of long genes via reduction of gene regulatory elements and an RNA splicing and DNA recombination-enabled multi-vector system.
The novel technology platform aims to solve transdermal delivery through formulation of AAV vectors into polymer devices. Gene therapy agents and pharmacological molecules are delivered directly into skin tissues via transient tissue microchannels, enabling rapid micro-scale mass transport that results in high local concentrations. Unlike conventional injections, this polymeric delivery system is minimally invasive due to the superficial administration, which reduces pain and host immune response, a critical advantage for enabling re-dosing. Taken together, the safety and efficacy of the platform further enable development of age-related aesthetic and quality-of-life treatments, targeting novel skin aging genes identified through a uniquely powerful data analytics approach.