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    Subretinal therapy offers promise of lighter treatment burden for AMD


    Intravitreal vs. subretinal gene therapy

    When the investigators considered the various available delivery routes, intravitreal delivery was considered easy to use, safe, and performed during an office visit. However, intravitreal delivery is considered to be less efficient by 100 to 1,000 times compared with subretinal delivery.

    Transduction via the intravitreal route is believed to be limited by the internal limiting membrane that acts as a barrier. In addition, and importantly, the pre-existing AAV neutralizing antibodies (NAbs) may neutralize gene therapy delivered intravitreally.

    “There is a high prevalence of NAbs, up to 70% exposure to AAV2 and 30-50% to AAV,” Dr. Heier added. “When gene therapy is delivered intravitreally, there may be limited or no transgene expression in patients with these antibodies.”

    In contrast, subretinal delivery is more invasive and requires a surgical procedure. However, this route is believed to deliver the best expression. The procedure has been reported to be safe in several trials.



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