Cargando…

Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo

Non-viral vectors, such as lipid-based nanoparticles (liposome-protamine-DNA complex [LPD]), could be used to deliver a functional gene to the retina to correct visual function and treat blindness. However, one of the limitations of LPD is the lack of cell specificity, as the retina is composed of s...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Yuhong, Rajala, Ammaji, Cao, Binrui, Ranjo-Bishop, Michelle, Agbaga, Martin-Paul, Mao, Chuanbin, Rajala, Raju V.S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955052/
https://www.ncbi.nlm.nih.gov/pubmed/27446487
http://dx.doi.org/10.7150/thno.15230
_version_ 1782443882646077440
author Wang, Yuhong
Rajala, Ammaji
Cao, Binrui
Ranjo-Bishop, Michelle
Agbaga, Martin-Paul
Mao, Chuanbin
Rajala, Raju V.S.
author_facet Wang, Yuhong
Rajala, Ammaji
Cao, Binrui
Ranjo-Bishop, Michelle
Agbaga, Martin-Paul
Mao, Chuanbin
Rajala, Raju V.S.
author_sort Wang, Yuhong
collection PubMed
description Non-viral vectors, such as lipid-based nanoparticles (liposome-protamine-DNA complex [LPD]), could be used to deliver a functional gene to the retina to correct visual function and treat blindness. However, one of the limitations of LPD is the lack of cell specificity, as the retina is composed of seven types of cells. If the same gene is expressed in multiple cell types or is absent from one desired cell type, LPD-mediated gene delivery to every cell may have off-target effects. To circumvent this problem, we have tested LPD-mediated gene delivery using various generalized, modified, and retinal cell-specific promoters. We achieved retinal pigment epithelium cell specificity with vitelliform macular dystrophy (VMD2), rod cell specificity with mouse rhodopsin, cone cell specificity with red/green opsin, and ganglion cell specificity with thymocyte antigen promoters. Here we show for the first time that cell-specific promoters enable lipid-based nanoparticles to deliver genes to specific cells of the retina in vivo. This work will inspire investigators in the field of lipid nanotechnology to couple cell-specific promoters to drive expression in a cell- and tissue-specific manner.
format Online
Article
Text
id pubmed-4955052
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-49550522016-07-21 Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo Wang, Yuhong Rajala, Ammaji Cao, Binrui Ranjo-Bishop, Michelle Agbaga, Martin-Paul Mao, Chuanbin Rajala, Raju V.S. Theranostics Research Paper Non-viral vectors, such as lipid-based nanoparticles (liposome-protamine-DNA complex [LPD]), could be used to deliver a functional gene to the retina to correct visual function and treat blindness. However, one of the limitations of LPD is the lack of cell specificity, as the retina is composed of seven types of cells. If the same gene is expressed in multiple cell types or is absent from one desired cell type, LPD-mediated gene delivery to every cell may have off-target effects. To circumvent this problem, we have tested LPD-mediated gene delivery using various generalized, modified, and retinal cell-specific promoters. We achieved retinal pigment epithelium cell specificity with vitelliform macular dystrophy (VMD2), rod cell specificity with mouse rhodopsin, cone cell specificity with red/green opsin, and ganglion cell specificity with thymocyte antigen promoters. Here we show for the first time that cell-specific promoters enable lipid-based nanoparticles to deliver genes to specific cells of the retina in vivo. This work will inspire investigators in the field of lipid nanotechnology to couple cell-specific promoters to drive expression in a cell- and tissue-specific manner. Ivyspring International Publisher 2016-06-17 /pmc/articles/PMC4955052/ /pubmed/27446487 http://dx.doi.org/10.7150/thno.15230 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Wang, Yuhong
Rajala, Ammaji
Cao, Binrui
Ranjo-Bishop, Michelle
Agbaga, Martin-Paul
Mao, Chuanbin
Rajala, Raju V.S.
Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo
title Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo
title_full Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo
title_fullStr Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo
title_full_unstemmed Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo
title_short Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo
title_sort cell-specific promoters enable lipid-based nanoparticles to deliver genes to specific cells of the retina in vivo
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955052/
https://www.ncbi.nlm.nih.gov/pubmed/27446487
http://dx.doi.org/10.7150/thno.15230
work_keys_str_mv AT wangyuhong cellspecificpromotersenablelipidbasednanoparticlestodelivergenestospecificcellsoftheretinainvivo
AT rajalaammaji cellspecificpromotersenablelipidbasednanoparticlestodelivergenestospecificcellsoftheretinainvivo
AT caobinrui cellspecificpromotersenablelipidbasednanoparticlestodelivergenestospecificcellsoftheretinainvivo
AT ranjobishopmichelle cellspecificpromotersenablelipidbasednanoparticlestodelivergenestospecificcellsoftheretinainvivo
AT agbagamartinpaul cellspecificpromotersenablelipidbasednanoparticlestodelivergenestospecificcellsoftheretinainvivo
AT maochuanbin cellspecificpromotersenablelipidbasednanoparticlestodelivergenestospecificcellsoftheretinainvivo
AT rajalarajuvs cellspecificpromotersenablelipidbasednanoparticlestodelivergenestospecificcellsoftheretinainvivo