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Antibody-Mediated Delivery of siRNAs for Anti-HIV Therapy

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Antiviral RNAi

Part of the book series: Methods in Molecular Biology ((MIMB,volume 721))

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.

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References

  1. Rossi, J. J., June, C. H., and Kohn, D. B. (2007) Genetic therapies against HIV, Nat Biotechnol 25, 1444–1454.

    Article  PubMed  CAS  Google Scholar 

  2. Hammond, S. M., Caudy, A. A., and Hannon, G. J. (2001) Post-transcriptional gene silencing by double-stranded RNA, Nat Rev Genet 2, 110–119.

    Article  PubMed  CAS  Google Scholar 

  3. Dykxhoorn, D. M., and Lieberman, J. (2006) Running interference: prospects and obstacles to using small interfering RNAs as small molecule drugs, Annu Rev Biomed Eng 8, 377–402.

    Article  PubMed  CAS  Google Scholar 

  4. Kim, D. H., and Rossi, J. J. (2007) Strategies for silencing human disease using RNA interference, Nat Rev Genet 8, 173–184.

    Article  PubMed  CAS  Google Scholar 

  5. Kim, S. S., Garg, H., Joshi, A., and Manjunath, N. (2009) Strategies for targeted nonviral delivery of siRNAs in vivo, Trends Mol Med 15, 491–500.

    Article  PubMed  CAS  Google Scholar 

  6. Song, E., Zhu, P., Lee, S. K., Chowdhury, D., Kussman, S., Dykxhoorn, D. M., Feng, Y., Palliser, D., Weiner, D. B., Shankar, P., Marasco, W. A., and Lieberman, J. (2005) Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors, Nat Biotechnol 23, 709–717.

    Article  PubMed  CAS  Google Scholar 

  7. Kumar, P., Ban, H. S., Kim, S. S., Wu, H., Pearson, T., Greiner, D. L., Laouar, A., Yao, J., Haridas, V., Habiro, K., Yang, Y. G., Jeong, J. H., Lee, K. Y., Kim, Y. H., Kim, S. W., Peipp, M., Fey, G. H., Manjunath, N., Shultz, L. D., Lee, S. K., and Shankar, P. (2008) T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice, Cell 134, 577–586.

    Article  PubMed  CAS  Google Scholar 

  8. Peer, D., Zhu, P., Carman, C. V., Lieberman, J., and Shimaoka, M. (2007) Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1, Proc Natl Acad Sci U S A 104, 4095–4100.

    Article  PubMed  CAS  Google Scholar 

  9. Peer, D., Park, E. J., Morishita, Y., Carman, C. V., and Shimaoka, M. (2008) Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target, Science 319, 627–630.

    Article  PubMed  CAS  Google Scholar 

  10. Subramanya, S., Kim, S. S., Abraham, S., Yao, J., Kumar, M., Kumar, P., Haridas, V., Lee, S. K., Shultz, L. D., Greiner, D., N, M., and Shankar, P. (2010) Targeted delivery of small interfering RNA to human dendritic cells to suppress dengue virus infection and associated proinflammatory cytokine production, J Virol 84, 2490–2501.

    Article  PubMed  CAS  Google Scholar 

  11. Kim, S. S., Peer, D., Kumar, P., Subramanya, S., Wu, H., Asthana, D., Habiro, K., Yang, Y. G., Manjunath, N., Shimaoka, M., and Shankar, P. (2010) RNAi-mediated CCR5 silencing by LFA-1-targeted nanoparticles prevents HIV infection in BLT mice, Mol Ther 18, 370–376.

    Article  PubMed  CAS  Google Scholar 

  12. Peipp, M., Kupers, H., Saul, D., Schlierf, B., Greil, J., Zunino, S. J., Gramatzki, M., and Fey, G. H. (2002) A recombinant CD7-specific single-chain immunotoxin is a potent inducer of apoptosis in acute leukemic T cells, Cancer Res 62, 2848–2855.

    PubMed  CAS  Google Scholar 

  13. Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., and Tuschl, T. (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells, Nature 411, 494–498.

    Article  PubMed  CAS  Google Scholar 

  14. Nakata, H., Maeda, K., Miyakawa, T., Shibayama, S., Matsuo, M., Takaoka, Y., Ito, M., Koyanagi, Y., and Mitsuya, H. (2005) Potent anti-R5 human immunodeficiency virus type 1 effects of a CCR5 antagonist, AK602/ONO4128/GW873140, in a novel human peripheral blood mononuclear cell nonobese diabetic-SCID, interleukin-2 receptor gamma-chain-knocked-out AIDS mouse model, J Virol 79, 2087–2096.

    Article  PubMed  CAS  Google Scholar 

  15. Ishikawa, F., Yasukawa, M., Lyons, B., Yoshida, S., Miyamoto, T., Yoshimoto, G., Watanabe, T., Akashi, K., Shultz, L. D., and Harada, M. (2005) Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice, Blood 106, 1565–1573.

    Article  PubMed  CAS  Google Scholar 

  16. Lan, P., Tonomura, N., Shimizu, A., Wang, S., and Yang, Y. G. (2006) Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation, Blood 108, 487–492.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Premlata Shankar .

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© 2011 Humana Press

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Kim, SS., Subramanya, S., Peer, D., Shimaoka, M., Shankar, P. (2011). Antibody-Mediated Delivery of siRNAs for Anti-HIV Therapy. In: van Rij, R. (eds) Antiviral RNAi. Methods in Molecular Biology, vol 721. Humana Press. https://doi.org/10.1007/978-1-61779-037-9_21

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  • DOI: https://doi.org/10.1007/978-1-61779-037-9_21

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-036-2

  • Online ISBN: 978-1-61779-037-9

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