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

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 Engineeri...

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Autores principales:	Kelley RA, Conley SM, Makkia R, Watson JN, Han Z, Cooper MJ, Naash MI
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	DNA nanoparticles non-human primate non-viral gene transfer baboon Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fdadab0133ff44f39eab1bec52312b40
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spelling	oai:doaj.org-article:fdadab0133ff44f39eab1bec52312b402021-12-02T02:49:14ZDNA nanoparticles are safe and nontoxic in non-human primate eyes1178-2013https://doaj.org/article/fdadab0133ff44f39eab1bec52312b402018-03-01T00:00:00Zhttps://www.dovepress.com/dna-nanoparticles-are-safe-and-nontoxic-in-non-human-primate-eyes-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ryan 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 transferKelley RAConley SMMakkia RWatson JNHan ZCooper MJNaash MIDove Medical PressarticleDNA nanoparticlesnon-human primatenon-viral gene transferbaboonMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 1361-1379 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNA nanoparticles non-human primate non-viral gene transfer baboon Medicine (General) R5-920
spellingShingle	DNA nanoparticles non-human primate non-viral gene transfer baboon Medicine (General) R5-920 Kelley RA Conley SM Makkia R Watson JN Han Z Cooper MJ Naash MI DNA nanoparticles are safe and nontoxic in non-human primate eyes
description	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
format	article
author	Kelley RA Conley SM Makkia R Watson JN Han Z Cooper MJ Naash MI
author_facet	Kelley RA Conley SM Makkia R Watson JN Han Z Cooper MJ Naash MI
author_sort	Kelley RA
title	DNA nanoparticles are safe and nontoxic in non-human primate eyes
title_short	DNA nanoparticles are safe and nontoxic in non-human primate eyes
title_full	DNA nanoparticles are safe and nontoxic in non-human primate eyes
title_fullStr	DNA nanoparticles are safe and nontoxic in non-human primate eyes
title_full_unstemmed	DNA nanoparticles are safe and nontoxic in non-human primate eyes
title_sort	dna nanoparticles are safe and nontoxic in non-human primate eyes
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/fdadab0133ff44f39eab1bec52312b40
work_keys_str_mv	AT kelleyra dnananoparticlesaresafeandnontoxicinnonhumanprimateeyes AT conleysm dnananoparticlesaresafeandnontoxicinnonhumanprimateeyes AT makkiar dnananoparticlesaresafeandnontoxicinnonhumanprimateeyes AT watsonjn dnananoparticlesaresafeandnontoxicinnonhumanprimateeyes AT hanz dnananoparticlesaresafeandnontoxicinnonhumanprimateeyes AT coopermj dnananoparticlesaresafeandnontoxicinnonhumanprimateeyes AT naashmi dnananoparticlesaresafeandnontoxicinnonhumanprimateeyes
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DNA nanoparticles are safe and nontoxic in non-human primate eyes

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