Novel engineered vectors (recombinant adeno-associated virus [vAAV]) may provide efficient targeting for photoreceptors avoiding risks of collateral damage.

Researchers at the Department of Ophthalmology, Ludwig-Maximilians-University, Munich, have reported results on novel engineered viral vectors aimed to efficiently target photoreceptors.  The research used a peptide-display library system to use several rounds of selection to generate capsid variants that can direct vectors to photoreceptors, and subsequently used the process in a model for colour vision.  The purpose of the research was aimed to fine tune the delivery of vectors to specific cells in the retina and use intravitreal delivery rather than sub-retinal delivery to avoid any mechanical disruption of the delicate retinal tissue.


In a number of retinal gene therapy procedures, a standard clinical practice for delivering a vector, via a surgical procedure, uses a sub-retinal insertion to target the therapy directed to the photoreceptors.  While this is a logical strategy, the mechanical disruption of the retina may cause collateral damage.  An alternative procedure aims to use an intravitreal injection to utilize the capsid coat of the vector as a “homing beacon” to target the vectors to photoreceptor cells.  In essence, this strategy uses a “post code” process as a molecular mechanism to much more selectively deliver an address to the physical location.  Intravitreal injection avoids disruption of sub-retinal injection which can damage impact on photoreceptors and the RPE.  In addition, the procedure also allows more surgical access, as commented by the researchers who stated that “intravitreal delivery of retinal gene therapies could be offered with potentially greater precision by a larger pool of professionals and without the need for specialised equipment. The development of novel rAAV vectors, capable of deep penetration of the retina layers after intravitreal administration, as we report here, could considerably improve patient outcome”.


The study used techniques for mouse, dog and human tissues and used a model of achromatopsia to deliver vectors providing a proof-of-concept result. An intravitreal injection with the gene Cnga3 delivery, engineered into an rAAV2, led to cone-specific expression of Cnga3 protein and rescued photopic cone responses in a Cnga3-/- mouse model of achromatopsia. While there is considerable work ahead for clinical translation of the strategy, this study indicates a significant impact for gene therapy and can present a potential paradigm shift for treatment for rescuing of several blinding human retinal dystrophies.  In conclusion to their paper, the researches commented that, ”[t]he use of these novel viral vectors could help improve patient outcome both in terms of efficiency and minimising the collateral damage evoked during administration. This could make gene therapies more successful and accessible to a wider patient pool, as the administration method is simpler and could be performed by any trained ophthalmologist”.