Ultrasound targeted microbubble destruction-mediated gene delivery system: application to therapy for ocular disease

Background: Ocular disorders have greatest potential for benefit from gene therapy. The major obstacle in the clinical application of gene therapy is not due to the lack of an ideal gene, but rather the lack of a clinically safe and efficient gene transfer method. Ultrasound (US) targeted microbubble destruction (UTMD)-mediated gene delivery system as a noninvasive gene transfer method is now widely used in gene therapy of cardiovascular disease, muscular tissue, and tumor, and proved to effectively enhance gene transfer in various studies in vitro and in vivo. However, it is just the beginning of application for ophthalmological disease.

Objective: Review the latest advancements in UTMD-mediated ocular gene transfection and discuss mechanisms of UTMD involved in gene transfection, obstacles, and limitations to the use of this technology, as well as the perspectives for future applications of UTMD-mediated gene delivery system.

Methods: Summarize published literature concerning UTMD-mediated ocular gene transfection.

Results: UTMD is an effective and safe gene delivery method of therapy for ocular diseases. Considerable progress has been made in US or UTMD-mediated viral and nonviral ocular gene delivery to retina, like recombinant adeno-associated virus (rAAV) and nanoparticles as nonviral gene carriers. In addition, UTMD has potential for producing the blood-retinal barrier opening and serves as a promising method for intravenous ocular gene delivery.

Conclusion: UTMD-mediated gene delivery system could effectively enhance gene transfer into ocular tissue. Though several problems remain to be solved, UTMD is a promising technology for the targeted gene therapy of ocular disease.