Antibody-linked spherical nucleic acids for cellular targeting

J Am Chem Soc. 2012 Oct 10;134(40):16488-91. doi: 10.1021/ja306854d. Epub 2012 Sep 28.

Abstract

Spherical nucleic acid (SNA) constructs are promising new single entity gene regulation materials capable of both cellular transfection and gene knockdown, but thus far are promiscuous structures, exhibiting excellent genetic but little cellular selectivity. In this communication, we describe a strategy to impart targeting capabilities to these constructs through noncovalent functionalization with a complementary antibody-DNA conjugate. As a proof-of-concept, we designed HER2-targeting SNAs and demonstrated that such structures exhibit cell type selectivity in terms of their uptake, and significantly greater gene knockdown in cells overexpressing the target antigen as compared to the analogous antibody-free and off-target materials.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology*
  • Cell Line, Tumor
  • DNA, Antisense / administration & dosage*
  • DNA, Antisense / chemistry
  • DNA, Antisense / genetics
  • DNA, Antisense / pharmacokinetics
  • Gene Knockdown Techniques
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / immunology*
  • Models, Molecular
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology*

Substances

  • Antibodies, Monoclonal
  • DNA, Antisense
  • Immunoconjugates
  • Receptor, ErbB-2