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Briefings in Functional Genomics and Proteomics Advance Access published online on July 31, 2007
Briefings in Functional Genomics and Proteomics, doi:10.1093/bfgp/elm015
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© Oxford University Press, 2007, All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Exploring cell type-specific internalizing antibodies for targeted delivery of siRNA

Bin Liu

Corresponding author. Bin Liu, Department of Anesthesia, 1001 Potrero Ave., Rm3C38, San Francisco, CA 94110, USA. Tel: +1 415 244 6973; Fax: +1 415 244 6276; E-mail: liub{at}anesthesia.ucsf.edu

A major challenge to the development of therapeutic small interfering RNAs (siRNAs) is specific and efficient in vivo delivery to target cells. Recent studies suggest that cell type-specific gene silencing in vivo can be achieved by combining siRNAs with cell type-specific affinity ligands such as monoclonal antibodies. The antibody-directed siRNA complex enters target cells through receptor endocytosis and is subsequently released to the cytosol to specifically silence target gene expression through biologically conserved RNA interference (RNAi) pathways. Antibody fragments fused with a small basic nucleic-acid-binding protein and antibody fragment-directed nanoimmunoliposomes are two examples of effective delivery vehicles in vivo. The demonstrated specificity of in vivo gene silencing and the lack of nonspecific immune activation and systemic toxicity encourage further development of therapies based on cell type-specific delivery of siRNA.

Keywords: Therapeutic siRNA, internalizing antibody, systemic delivery, cell type-specific gene silencing


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