Antibody-mediated delivery of siRNAs for anti-HIV therapy

Methods Mol Biol. 2011:721:339-53. doi: 10.1007/978-1-61779-037-9_21.

Abstract

RNA interference (RNAi) is a potent and specific gene silencing mechanism that utilizes small -double-stranded RNA intermediates (small interfering RNAs or siRNAs) to target homologous mRNA sequences for degradation. The therapeutic potential of RNAi for HIV infection has been demonstrated in many studies. However, successful clinical application of RNAi is contingent on developing practical strategies to deliver siRNA to the desired target cells and tissues. Recently, there has been significant progress towards developing reagents that selectively deliver exogenous siRNA to immune cells that are targeted by HIV or involved in viral pathogenesis, such as T cells, macrophages, and dendritic cells. Here, we describe details of two antibody-based strategies for systemic delivery of siRNA either specifically to T cells via the CD7 receptor or to multiple immune cell types via LFA-1, present on all leukocytes.

MeSH terms

  • Animals
  • Antibody Specificity
  • Antigens, CD7 / immunology
  • Arginine
  • Base Sequence
  • Cloning, Molecular
  • Drug Carriers / chemistry
  • Drug Carriers / isolation & purification
  • Drug Carriers / metabolism*
  • Drug Delivery Systems*
  • Escherichia coli / genetics
  • HIV / genetics*
  • HIV / physiology*
  • HIV Infections / genetics
  • HIV Infections / therapy
  • Humans
  • Integrins / metabolism
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Mice
  • Models, Molecular
  • Molecular Targeted Therapy
  • Nanoparticles / chemistry
  • Nucleic Acid Conformation
  • Protein Refolding
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / immunology*
  • Single-Chain Antibodies / isolation & purification
  • Single-Chain Antibodies / metabolism*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology
  • Transfection

Substances

  • Antigens, CD7
  • Drug Carriers
  • Integrins
  • Lymphocyte Function-Associated Antigen-1
  • RNA, Small Interfering
  • Single-Chain Antibodies
  • Arginine