Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.

<h4>Background</h4>The eye is an excellent candidate for gene therapy as it is immune privileged and much of the disease-causing genetics are well understood. Towards this goal, we evaluated the efficiency of compacted DNA nanoparticles as a system for non-viral gene transfer to ocular t...

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Main Authors: Rafal Farjo, Jeff Skaggs, Alexander B Quiambao, Mark J Cooper, Muna I Naash
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2006-12-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000038&type=printable
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author Rafal Farjo
Jeff Skaggs
Alexander B Quiambao
Mark J Cooper
Muna I Naash
author_facet Rafal Farjo
Jeff Skaggs
Alexander B Quiambao
Mark J Cooper
Muna I Naash
author_sort Rafal Farjo
collection DOAJ
description <h4>Background</h4>The eye is an excellent candidate for gene therapy as it is immune privileged and much of the disease-causing genetics are well understood. Towards this goal, we evaluated the efficiency of compacted DNA nanoparticles as a system for non-viral gene transfer to ocular tissues. The compacted DNA nanoparticles examined here have been shown to be safe and effective in a human clinical trial, have no theoretical limitation on plasmid size, do not provoke immune responses, and can be highly concentrated.<h4>Methods and findings</h4>Here we show that these nanoparticles can be targeted to different tissues within the eye by varying the site of injection. Almost all cell types of the eye were capable of transfection by the nanoparticle and produced robust levels of gene expression that were dose-dependent. Most impressively, subretinal delivery of these nanoparticles transfected nearly all of the photoreceptor population and produced expression levels almost equal to that of rod opsin, the highest expressed gene in the retina.<h4>Conclusions</h4>As no deleterious effects on retinal function were observed, this treatment strategy appears to be clinically viable and provides a highly efficient non-viral technology to safely deliver and express nucleic acids in the retina and other ocular tissues.
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spelling doaj-art-e6f45367c3b44182a5ea86c510b68ce92025-08-20T03:22:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032006-12-011e3810.1371/journal.pone.0000038Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.Rafal FarjoJeff SkaggsAlexander B QuiambaoMark J CooperMuna I Naash<h4>Background</h4>The eye is an excellent candidate for gene therapy as it is immune privileged and much of the disease-causing genetics are well understood. Towards this goal, we evaluated the efficiency of compacted DNA nanoparticles as a system for non-viral gene transfer to ocular tissues. The compacted DNA nanoparticles examined here have been shown to be safe and effective in a human clinical trial, have no theoretical limitation on plasmid size, do not provoke immune responses, and can be highly concentrated.<h4>Methods and findings</h4>Here we show that these nanoparticles can be targeted to different tissues within the eye by varying the site of injection. Almost all cell types of the eye were capable of transfection by the nanoparticle and produced robust levels of gene expression that were dose-dependent. Most impressively, subretinal delivery of these nanoparticles transfected nearly all of the photoreceptor population and produced expression levels almost equal to that of rod opsin, the highest expressed gene in the retina.<h4>Conclusions</h4>As no deleterious effects on retinal function were observed, this treatment strategy appears to be clinically viable and provides a highly efficient non-viral technology to safely deliver and express nucleic acids in the retina and other ocular tissues.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000038&type=printable
spellingShingle Rafal Farjo
Jeff Skaggs
Alexander B Quiambao
Mark J Cooper
Muna I Naash
Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.
PLoS ONE
title Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.
title_full Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.
title_fullStr Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.
title_full_unstemmed Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.
title_short Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.
title_sort efficient non viral ocular gene transfer with compacted dna nanoparticles
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000038&type=printable
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AT alexanderbquiambao efficientnonviraloculargenetransferwithcompacteddnananoparticles
AT markjcooper efficientnonviraloculargenetransferwithcompacteddnananoparticles
AT munainaash efficientnonviraloculargenetransferwithcompacteddnananoparticles