Ocular Gene Therapy Core

The NEI Ocular Gene Therapy Core (OGTC) assists intramural investigators with multiple aspects of therapeutic studies for retinal diseases. The Core has strong expertise in the design, construction, packaging and purification of adeno-associated virus (AAV) vectors and provides a broad selection of capsid serotypes. AAV vectors are currently the most effective means to transduce gene constructs into retinal cells in vivo via subretinal injections, and as such are being used widely in developing gene therapies and in basic research. The Core can also advise on the use of AAV vectors and help with subretinal delivery.

While traditionally rodent models have typically been the recipient of choice for AAV-vector mediated gene transduction, advances in stem cell derived retinal organoids are increasingly making these a new and viable alternative. The Core utilizes both mouse and human iPSCs to create retinal organoids. These organoids are complex laminated structures resembling those of the in vivo mouse and human retinas. Investigators are encouraged to employ an organoid based platform to address some of their research questions, where appropriate, before resorting to the use of animal models. Such an approach aligns with NIH’s goal of reducing animal use in research and may help alleviate some of the fiscal and regulatory burdens on the investigator. Questions appropriate for the organoid models may include validation of vector design, vector transduction efficiency, effectiveness of a chosen promoter, biochemical and functional analyses of expressed transgenes, and phenotype modification in the targeted retinal cells following gene delivery. Testing of candidate therapeutic compounds in organoids is also a viable option.

Services

The Core is dedicated to providing valuable resources to the intramural research community working on retinal disease research. Investigators planning to use AAV vectors or retinal organoids in their research projects are encouraged to reach out to the Core staff and initiate a discussion. The Core will assist in all aspects of AAV vector production from design, cloning and packaging. The Core also has a long list of commonly used vectors which may be provided off shelf. Core staff will train users in subretinal and intravitreal injection techniques when needed.

The Core will provide mouse and human retinal organoids of varying stage of development upon request, and when space permitting can help conduct tests on organoids in the Core. Core staff is conducting ongoing research to optimize organoid production and maintenance aiming to streamline the procedure, cut costs and improve reproducibility.

Additional Information (PDF)