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Nonviral PDMAEMA Vectors Efficiently Express PDE6beta in a Mouse Model of Retinitis Pigmentosa

Bitoque, D. B.; Calado, S. M.; Rosa da Costa, A. M.; Silva, G.

2023-05-09 bioengineering
10.1101/2023.05.04.538567 bioRxiv
Show abstract

Retinitis Pigmentosa (RP) is one of main causes of inherited blindness, with about 6% of cases caused by a single mutation in the PDE6{beta} gene, making it an ideal candidate for a gene therapy intervention. Gene therapy has been shown to restore normal retinal and visual function in other monogenic diseases, such as Lebers Congenital Amaurosis and choroideremia, and RP could benefit from a similar therapeutic approach. Our goal was to combine efficient nonviral vectors and gene expression systems to express the PDE6{beta} gene in the retina of a mouse model of Retinitis Pigmentosa. We have firstly validated the potential of PDMAEMA polyplexes as a nonviral vector by subretinal injection, which were shown to efficiently promote gene expression in the RPE layer of the adult mouse retina. We have then produced polyplexes of PDMAEMA with a replicating plasmid expressing the PDE6{beta} gene and administered the polyplexes via subretinal injection in the rd10 mouse. We have observed that PDMAEMA polyplexes were able to efficiently enter the target retinal pigment epithelium cells and rapidly express the PDE6{beta} gene in the mouse retina, thus confirming their potential as nonviral vectors for retinal gene therapy.

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