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DNA nanoparticles are safe and nontoxic in non-human primate eyes

Authors Kelley RA, Conley SM, Makkia R, Watson JN, Han Z, Cooper MJ, Naash MI

Received 14 November 2017

Accepted for publication 23 December 2017

Published 8 March 2018 Volume 2018:13 Pages 1361—1379


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 5

Editor who approved publication: Dr Thomas Webster

Ryan A Kelley,1 Shannon M Conley,1 Rasha Makkia,1 Jamie N Watson,1 Zongchao Han,1 Mark J Cooper,2 Muna I Naash3

1Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 2Copernicus Therapeutics, Inc., Cleveland, OH, USA; 3Department of Biomedical Engineering, University of Houston, Houston, TX, USA

Introduction: DNA nanoparticles (NPs) comprising polylysine conjugated to polyethylene glycol efficiently target murine photoreceptors and the retinal pigment epithelium (RPE) and lead to long-term phenotypic improvement in models of retinal degeneration. Advancing this technology requires testing in a large animal model, particularly with regard to safety. So, herein we evaluate NPs in non-human primates (baboon).
Methods and results: NPs with plasmids carrying GFP and a ubiquitous, RPE-specific, or photoreceptor-specific promoter were delivered by either subretinal or intravitreal injection. We detected GFP message and protein in the retina/RPE from eyes dosed with NPs carrying ubiquitously expressed and RPE-specific vectors, and GFP message in eyes injected with NPs carrying photoreceptor-specific vectors. Importantly, we observed NP DNA in the retina/RPE following intravitreal injection, indicating the inner limiting membrane does not prevent NP diffusion into the outer retina. We did not observe any adverse events in any baboon, and there were no NP-associated changes in retinal function. Furthermore, no systemic or local inflammatory reaction to the vectors/injections was observed, and no NP DNA was found outside the eye.
Conclusion: Taken together with the well-established rodent safety and efficacy data, these findings suggest that DNA NPs may be a safe and potentially clinically viable nonviral ocular therapy platform for retinal diseases.

Keywords: DNA nanoparticles, non-human primate, nonviral gene transfer, baboon, gene therapy, safety, ocular gene transfer

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