Cargando…

Suprachoroidally Delivered DNA Nanoparticles Transfect Retina and Retinal Pigment Epithelium/Choroid in Rabbits

PURPOSE: This study evaluated ocular tolerability and transfectability of nonviral DNA nanoparticles (DNPs) after microneedle-based suprachoroidal (SC) administration, in comparison to subretinal (SR) administration. METHODS: The DNPs consisted of a single copy of plasmid DNA with a polyubiquitin C/...

Descripción completa

Detalles Bibliográficos
Autores principales: Kansara, Viral S., Cooper, Mark, Sesenoglu-Laird, Ozge, Muya, Leroy, Moen, Robert, Ciulla, Thomas A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745627/
https://www.ncbi.nlm.nih.gov/pubmed/33364076
http://dx.doi.org/10.1167/tvst.9.13.21
_version_ 1783624645494177792
author Kansara, Viral S.
Cooper, Mark
Sesenoglu-Laird, Ozge
Muya, Leroy
Moen, Robert
Ciulla, Thomas A.
author_facet Kansara, Viral S.
Cooper, Mark
Sesenoglu-Laird, Ozge
Muya, Leroy
Moen, Robert
Ciulla, Thomas A.
author_sort Kansara, Viral S.
collection PubMed
description PURPOSE: This study evaluated ocular tolerability and transfectability of nonviral DNA nanoparticles (DNPs) after microneedle-based suprachoroidal (SC) administration, in comparison to subretinal (SR) administration. METHODS: The DNPs consisted of a single copy of plasmid DNA with a polyubiquitin C/luciferase transcriptional cassette compacted with 10 kDa PEG-substituted lysine 30-mer peptides (CK30PEG10k). New Zealand White rabbits (n = 4 per group) received a unilateral SC injection (0.1 mL via a microneedle technique) of ellipsoid-shaped DNPs, rod-shaped DNPs, or saline (negative control). A cohort of rabbits (n = 4) also received a single unilateral SR injection (0.05 mL via a transvitreal approach) of rod-shaped DNPs. At day 7, luciferase activity was measured in the retina and retinal pigment epithelium (RPE)–choroid via bioluminescence assay. A cohort of rabbits received a SC injection of analogous DNPs to assess spread of DNP injectate in the suprachoroidal space (SCS) via optical coherent tomography and histology. RESULTS: Suprachoroidal injection of DNPs resulted in reversible opening of the SCS circumferentially and posteriorly and was generally well tolerated, with no significant ocular examination score changes, intraocular pressure abnormalities, or changes in electroretinography amplitudes on day 7 compared to the baseline. High luciferase activity was observed in the retina and RPE-choroid of eyes that received SC DNPs (rod and ellipsoid shape) and SR DNPs (rod shape) compared to controls. The mean luciferase activity in RPE-choroid and retina was comparable between SC and SR administrations. Transfection in the RPE-choroid was approximately 10-fold higher than in the retina after either SC or SR administration of DNPs. CONCLUSIONS: Suprachoroidal and SR administration of DNPs resulted in comparable transfection of retina and RPE-choroid. TRANSLATIONAL RELEVANCE: Suprachoroidal delivery of DNPs offers the potential to precisely target chorioretinal tissues while avoiding surgical risks associated with SR injection, and it may offer an office-based nonsurgical gene therapy option for the treatment of retinal diseases.
format Online
Article
Text
id pubmed-7745627
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher The Association for Research in Vision and Ophthalmology
record_format MEDLINE/PubMed
spelling pubmed-77456272020-12-23 Suprachoroidally Delivered DNA Nanoparticles Transfect Retina and Retinal Pigment Epithelium/Choroid in Rabbits Kansara, Viral S. Cooper, Mark Sesenoglu-Laird, Ozge Muya, Leroy Moen, Robert Ciulla, Thomas A. Transl Vis Sci Technol Article PURPOSE: This study evaluated ocular tolerability and transfectability of nonviral DNA nanoparticles (DNPs) after microneedle-based suprachoroidal (SC) administration, in comparison to subretinal (SR) administration. METHODS: The DNPs consisted of a single copy of plasmid DNA with a polyubiquitin C/luciferase transcriptional cassette compacted with 10 kDa PEG-substituted lysine 30-mer peptides (CK30PEG10k). New Zealand White rabbits (n = 4 per group) received a unilateral SC injection (0.1 mL via a microneedle technique) of ellipsoid-shaped DNPs, rod-shaped DNPs, or saline (negative control). A cohort of rabbits (n = 4) also received a single unilateral SR injection (0.05 mL via a transvitreal approach) of rod-shaped DNPs. At day 7, luciferase activity was measured in the retina and retinal pigment epithelium (RPE)–choroid via bioluminescence assay. A cohort of rabbits received a SC injection of analogous DNPs to assess spread of DNP injectate in the suprachoroidal space (SCS) via optical coherent tomography and histology. RESULTS: Suprachoroidal injection of DNPs resulted in reversible opening of the SCS circumferentially and posteriorly and was generally well tolerated, with no significant ocular examination score changes, intraocular pressure abnormalities, or changes in electroretinography amplitudes on day 7 compared to the baseline. High luciferase activity was observed in the retina and RPE-choroid of eyes that received SC DNPs (rod and ellipsoid shape) and SR DNPs (rod shape) compared to controls. The mean luciferase activity in RPE-choroid and retina was comparable between SC and SR administrations. Transfection in the RPE-choroid was approximately 10-fold higher than in the retina after either SC or SR administration of DNPs. CONCLUSIONS: Suprachoroidal and SR administration of DNPs resulted in comparable transfection of retina and RPE-choroid. TRANSLATIONAL RELEVANCE: Suprachoroidal delivery of DNPs offers the potential to precisely target chorioretinal tissues while avoiding surgical risks associated with SR injection, and it may offer an office-based nonsurgical gene therapy option for the treatment of retinal diseases. The Association for Research in Vision and Ophthalmology 2020-12-15 /pmc/articles/PMC7745627/ /pubmed/33364076 http://dx.doi.org/10.1167/tvst.9.13.21 Text en Copyright 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Article
Kansara, Viral S.
Cooper, Mark
Sesenoglu-Laird, Ozge
Muya, Leroy
Moen, Robert
Ciulla, Thomas A.
Suprachoroidally Delivered DNA Nanoparticles Transfect Retina and Retinal Pigment Epithelium/Choroid in Rabbits
title Suprachoroidally Delivered DNA Nanoparticles Transfect Retina and Retinal Pigment Epithelium/Choroid in Rabbits
title_full Suprachoroidally Delivered DNA Nanoparticles Transfect Retina and Retinal Pigment Epithelium/Choroid in Rabbits
title_fullStr Suprachoroidally Delivered DNA Nanoparticles Transfect Retina and Retinal Pigment Epithelium/Choroid in Rabbits
title_full_unstemmed Suprachoroidally Delivered DNA Nanoparticles Transfect Retina and Retinal Pigment Epithelium/Choroid in Rabbits
title_short Suprachoroidally Delivered DNA Nanoparticles Transfect Retina and Retinal Pigment Epithelium/Choroid in Rabbits
title_sort suprachoroidally delivered dna nanoparticles transfect retina and retinal pigment epithelium/choroid in rabbits
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745627/
https://www.ncbi.nlm.nih.gov/pubmed/33364076
http://dx.doi.org/10.1167/tvst.9.13.21
work_keys_str_mv AT kansaravirals suprachoroidallydelivereddnananoparticlestransfectretinaandretinalpigmentepitheliumchoroidinrabbits
AT coopermark suprachoroidallydelivereddnananoparticlestransfectretinaandretinalpigmentepitheliumchoroidinrabbits
AT sesenoglulairdozge suprachoroidallydelivereddnananoparticlestransfectretinaandretinalpigmentepitheliumchoroidinrabbits
AT muyaleroy suprachoroidallydelivereddnananoparticlestransfectretinaandretinalpigmentepitheliumchoroidinrabbits
AT moenrobert suprachoroidallydelivereddnananoparticlestransfectretinaandretinalpigmentepitheliumchoroidinrabbits
AT ciullathomasa suprachoroidallydelivereddnananoparticlestransfectretinaandretinalpigmentepitheliumchoroidinrabbits