Theranostics 2016; 6(10):1514-1527. doi:10.7150/thno.15230

Research Paper

Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo

Yuhong Wang1,4*, Ammaji Rajala1,4*, Binrui Cao5, Michelle Ranjo-Bishop1,4, Martin-Paul Agbaga1,4, Chuanbin Mao5,6✉, Raju V.S. Rajala1,2,3,4✉

1. Departments of Ophthalmology, University of Oklahoma Health Sciences Center;
2. Departments of Physiology, University of Oklahoma Health Sciences Center;
3. Departments of Cell Biology, University of Oklahoma Health Sciences Center;
4. Dean McGee Eye Institute, Oklahoma City, OK 73104, USA;
5. Department of Chemistry and Biochemistry, University of Oklahoma, Stephenson Life Science Research Center, Norman, OK 73019, USA;
6. School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China.
* Y.W. and A.R. equally contributed to this work.


Non-viral vectors, such as lipid-based nanoparticles (liposome-protamine-DNA complex [LPD]), could be used to deliver a functional gene to the retina to correct visual function and treat blindness. However, one of the limitations of LPD is the lack of cell specificity, as the retina is composed of seven types of cells. If the same gene is expressed in multiple cell types or is absent from one desired cell type, LPD-mediated gene delivery to every cell may have off-target effects. To circumvent this problem, we have tested LPD-mediated gene delivery using various generalized, modified, and retinal cell-specific promoters. We achieved retinal pigment epithelium cell specificity with vitelliform macular dystrophy (VMD2), rod cell specificity with mouse rhodopsin, cone cell specificity with red/green opsin, and ganglion cell specificity with thymocyte antigen promoters. Here we show for the first time that cell-specific promoters enable lipid-based nanoparticles to deliver genes to specific cells of the retina in vivo. This work will inspire investigators in the field of lipid nanotechnology to couple cell-specific promoters to drive expression in a cell- and tissue-specific manner.

Keywords: Lipid nanoparticles, Gene therapy, Retina, Retinal pigment epithelium, Ganglion cells, Cell-specific promoters.

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How to cite this article:
Wang Y, Rajala A, Cao B, Ranjo-Bishop M, Agbaga MP, Mao C, Rajala RVS. Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo. Theranostics 2016; 6(10):1514-1527. doi:10.7150/thno.15230. Available from