_version_ 1811081340981870592
author Harris, Todd J.
Green, Jordan J.
Fung, Peter W.
Langer, Robert S
Anderson, Daniel Griffith
Bhatia, Sangeeta N
author2 Harvard University--MIT Division of Health Sciences and Technology
author_facet Harvard University--MIT Division of Health Sciences and Technology
Harris, Todd J.
Green, Jordan J.
Fung, Peter W.
Langer, Robert S
Anderson, Daniel Griffith
Bhatia, Sangeeta N
author_sort Harris, Todd J.
collection MIT
description Author Manuscript: 2010 August 1.
first_indexed 2024-09-23T11:45:13Z
format Article
id mit-1721.1/75302
institution Massachusetts Institute of Technology
language en_US
last_indexed 2024-09-23T11:45:13Z
publishDate 2012
publisher Elsevier
record_format dspace
spelling mit-1721.1/753022022-10-01T05:43:54Z Tissue-Specific Gene Delivery via Nanoparticle Coating Harris, Todd J. Green, Jordan J. Fung, Peter W. Langer, Robert S Anderson, Daniel Griffith Bhatia, Sangeeta N Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Koch Institute for Integrative Cancer Research at MIT Langer, Robert Anderson, Daniel G. Bhatia, Sangeeta N. Author Manuscript: 2010 August 1. The use of biomaterials for gene delivery can potentially avoid many of the safety concerns with viral gene delivery. However, the efficacy of polymeric gene delivery methods is low, particularly in vivo. One significant concern is that the interior and exterior composition of polymeric gene delivery nanoparticles are often coupled, with a single polymer backbone governing all functions from biophysical properties of the polymer/DNA particle to DNA condensation and release. In this work we develop electrostatically adsorbed poly(glutamic acid)-based peptide coatings to alter the exterior composition of a core gene delivery particle and thereby affect tissue-specificity of gene delivery function in vivo. We find that with all coating formulations tested, the coatings reduce potential toxicity associated with uncoated cationic gene delivery nanoparticles following systemic injection. Particles coated with a low 2.5:1 peptide:DNA weight ratio (w/w) form large 2 μ sized particles in the presence of serum that can facilitate specific gene delivery to the liver. The same particles coated at a higher 20:1 w/w form small 200 nm particles in the presence of serum that can facilitate specific gene delivery to the spleen and bone marrow. Thus, variations in nanoparticle peptide coating density can alter the tissue-specificity of gene delivery in vivo. National Institutes of Health (U.S.) (BRP: 1R01CA124427-01) National Institutes of Health (U.S.) (EB 000244) National Institutes of Health (U.S.) (U54 CA119349-01) David & Lucile Packard Foundation (Fellowship 1999-1453A) 2012-12-07T21:12:49Z 2012-12-07T21:12:49Z 2009-10 2009-08 Article http://purl.org/eprint/type/JournalArticle 0142-9612 1878-5905 http://hdl.handle.net/1721.1/75302 Harris, Todd J. et al. “Tissue-specific Gene Delivery via Nanoparticle Coating.” Biomaterials 31.5 (2010): 998–1006. https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0002-1293-2097 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1016/j.biomaterials.2009.10.012 Biomaterials Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Elsevier PMC
spellingShingle Harris, Todd J.
Green, Jordan J.
Fung, Peter W.
Langer, Robert S
Anderson, Daniel Griffith
Bhatia, Sangeeta N
Tissue-Specific Gene Delivery via Nanoparticle Coating
title Tissue-Specific Gene Delivery via Nanoparticle Coating
title_full Tissue-Specific Gene Delivery via Nanoparticle Coating
title_fullStr Tissue-Specific Gene Delivery via Nanoparticle Coating
title_full_unstemmed Tissue-Specific Gene Delivery via Nanoparticle Coating
title_short Tissue-Specific Gene Delivery via Nanoparticle Coating
title_sort tissue specific gene delivery via nanoparticle coating
url http://hdl.handle.net/1721.1/75302
https://orcid.org/0000-0001-5629-4798
https://orcid.org/0000-0002-1293-2097
https://orcid.org/0000-0003-4255-0492
work_keys_str_mv AT harristoddj tissuespecificgenedeliveryviananoparticlecoating
AT greenjordanj tissuespecificgenedeliveryviananoparticlecoating
AT fungpeterw tissuespecificgenedeliveryviananoparticlecoating
AT langerroberts tissuespecificgenedeliveryviananoparticlecoating
AT andersondanielgriffith tissuespecificgenedeliveryviananoparticlecoating
AT bhatiasangeetan tissuespecificgenedeliveryviananoparticlecoating