Less invasive gene delivery for eyes

Eyes are a popular organ of choice for gene therapies, thanks to their accessibility and limited immune activity. Now, physicians are developing an even less invasive method – possibly reducing ocular genetic therapy to an outpatient setting.

Current clinical trials for eye diseases rely mainly on a surgical procedure, called subretinal injections. As the treatment must be repeated every few weeks, such frequent surgery poses numerous possible problems.

A new method aims to replace surgery with microneedle injections. Instead of targeting subretina, needles will reach space between sclera and choroid, called suprachoroidal space. Team from Johns Hopkins University and Regenxbio tested the procedure in 10 rats, a pig, and in 3 monkeys. Inject adeno-associated viruses successfully moved to the retina and expressed experimental genes – in this case, GFP genes with fluorescent, easily visible activity.

Although two variants of viruses (AAV8 and AAV9) functioned without problems, the third variant (AAV2) had difficulty with transfer from suprachoroidal space to the retina. That finding suggests that not all viruses are capable of spreading from that region of an eye.

Scientists predict that reaching most of the retinal tissue will require four injections (each quadrant of an eye).

Our hope is that with suprachoroidal injections, patients can just walk into a clinic and get their vision-saving treatment without worrying about many of the complications that come with subretinal injections.

Peter Campochiaro, corresponding author of the study

Regenxbio company currently conducts clinical trials for wet age-related macular degeneration (anti-VEGF therapy) via subretinal injections. Current preclinical study can be expected as the basis of similar clinical trials with the new method in humans.

Source: Ding, K., Shen, J., Hafiz, Z., Hackett, S. F., e Silva, R. L., Khan, M., … & Van Everen, S. (2019). AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression. The Journal of clinical investigation. Doi:10.1172/JCI129085.

Leave a Reply