Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Site-specific antibody-polymer conjugates for siRNA delivery

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Lu, H.
  • Wang, D.
  • Kazane, Stephanie Ann
  • Javahishvili, T.
  • Tian, F.
  • Song, F.
  • Sellers, A.
  • Barnett, B.
  • Schultz, Peter

publication date

  • September 2013

journal

  • Journal of the American Chemical Society  Journal

abstract

  • We describe here the development of site-specific antibody-polymer conjugates (APCs) for the selective delivery of small interference RNAs (siRNAs) to target cells. APCs were synthesized in good yields by conjugating an aminooxy-derivatized cationic block copolymer to an anti-HER2 Fab or full-length IgG by means of genetically encoded p-acetyl phenylalanine (pAcF). The APCs all showed binding affinity comparable to that of HER2 as their native counterparts and no significant cellular cytotoxicity. Mutant S202-pAcF Fab and Q389-pAcF IgG polymer conjugates specifically delivered siRNAs to HER2(+) cells and mediated potent gene silencing at both the mRNA and protein levels. However, a mutant A121-pAcF IgG polymer conjugate, despite its high binding affinity to HER2 antigen, did not induce a significant RNA interference response in HER2(+) cells, presumably due to steric interference with antigen binding and internalization. These results highlight the importance of conjugation site on the activity of antibody-polymer-based therapeutics and suggest that such chemically defined APCs may afford a useful targeted delivery platform for siRNAs or other nucleic acid-based therapies.

subject areas

  • Antibodies
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Survival
  • Drug Delivery Systems
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Humans
  • Immunoconjugates
  • Microscopy, Confocal
  • Polymers
  • RNA, Small Interfering
  • Receptor, ErbB-2
  • Trastuzumab
scroll to property group menus

Identity

PubMed Central ID

  • PMC3955097

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja4059525

PubMed ID

  • 23924037
scroll to property group menus

Additional Document Info

start page

  • 13885

end page

  • 13891

volume

  • 135

issue

  • 37

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support