Zhou, J., Neff, C. P., Liu, X., Zhang, J., Li, H., Smith, D. D., Swiderski, P., Aboellail, T., Huang, Y., Du, Q., Liang, Z., Peng, L., Akkina, R., & Rossi, J. J. (2011). Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice. Molecular Therapy, 19(12), 2228-2238. https://doi.org/10.1038/mt.2011.207
Zhou, Jiehua ; Neff, C. Preston ; Liu, Xiaoxuan et al. / Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice. In: Molecular Therapy. 2011 ; Vol. 19, No. 12. pp. 2228-2238.
@article{b0ba61ef2f094671aaad7a1cadb60af9,
title = "Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice",
abstract = "We evaluated the in vivo efficacy of structurally flexible, cationic PAMAM dendrimers as a small interfering RNA (siRNA) delivery system in a Rag2 / γc / (RAG-hu) humanized mouse model for HIV-1 infection. HIV-infected humanized Rag2 / γc / mice (RAG-hu) were injected intravenously (i.v.) with dendrimer-siRNA nanoparticles consisting of a cocktail of dicer substrate siRNAs (dsiRNAs) targeting both viral and cellular transcripts. We report in this study that the dendrimer-dsiRNA treatment suppressed HIV-1 infection by several orders of magnitude and protected against viral induced CD4 T-cell depletion. We also demonstrated that follow-up injections of the dendrimer-cocktailed dsiRNAs following viral rebound resulted in complete inhibition of HIV-1 titers. Biodistribution studies demonstrate that the dendrimer-dsiRNAs preferentially accumulate in peripheral blood mononuclear cells (PBMCs) and liver and do not exhibit any discernable toxicity. These data demonstrate for the first time efficacious combinatorial delivery of anti-host and-viral siRNAs for HIV-1 treatment in vivo. The dendrimer delivery approach therefore represents a promising method for systemic delivery of combinations of siRNAs for treatment of HIV-1 infection.",
author = "Jiehua Zhou and Neff, {C. Preston} and Xiaoxuan Liu and Jane Zhang and Haitang Li and Smith, {David D.} and Piotr Swiderski and Tawfik Aboellail and Yuanyu Huang and Quan Du and Zicai Liang and Ling Peng and Ramesh Akkina and Rossi, {John J.}",
year = "2011",
month = dec,
doi = "10.1038/mt.2011.207",
language = "English",
volume = "19",
pages = "2228--2238",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Cell Press",
number = "12",
}
Zhou, J, Neff, CP, Liu, X, Zhang, J, Li, H, Smith, DD, Swiderski, P, Aboellail, T, Huang, Y, Du, Q, Liang, Z, Peng, L, Akkina, R & Rossi, JJ 2011, 'Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice', Molecular Therapy, vol. 19, no. 12, pp. 2228-2238. https://doi.org/10.1038/mt.2011.207
Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice. / Zhou, Jiehua; Neff, C. Preston; Liu, Xiaoxuan et al.
In:
Molecular Therapy, Vol. 19, No. 12, 12.2011, p. 2228-2238.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice
AU - Zhou, Jiehua
AU - Neff, C. Preston
AU - Liu, Xiaoxuan
AU - Zhang, Jane
AU - Li, Haitang
AU - Smith, David D.
AU - Swiderski, Piotr
AU - Aboellail, Tawfik
AU - Huang, Yuanyu
AU - Du, Quan
AU - Liang, Zicai
AU - Peng, Ling
AU - Akkina, Ramesh
AU - Rossi, John J.
PY - 2011/12
Y1 - 2011/12
N2 - We evaluated the in vivo efficacy of structurally flexible, cationic PAMAM dendrimers as a small interfering RNA (siRNA) delivery system in a Rag2 / γc / (RAG-hu) humanized mouse model for HIV-1 infection. HIV-infected humanized Rag2 / γc / mice (RAG-hu) were injected intravenously (i.v.) with dendrimer-siRNA nanoparticles consisting of a cocktail of dicer substrate siRNAs (dsiRNAs) targeting both viral and cellular transcripts. We report in this study that the dendrimer-dsiRNA treatment suppressed HIV-1 infection by several orders of magnitude and protected against viral induced CD4 T-cell depletion. We also demonstrated that follow-up injections of the dendrimer-cocktailed dsiRNAs following viral rebound resulted in complete inhibition of HIV-1 titers. Biodistribution studies demonstrate that the dendrimer-dsiRNAs preferentially accumulate in peripheral blood mononuclear cells (PBMCs) and liver and do not exhibit any discernable toxicity. These data demonstrate for the first time efficacious combinatorial delivery of anti-host and-viral siRNAs for HIV-1 treatment in vivo. The dendrimer delivery approach therefore represents a promising method for systemic delivery of combinations of siRNAs for treatment of HIV-1 infection.
AB - We evaluated the in vivo efficacy of structurally flexible, cationic PAMAM dendrimers as a small interfering RNA (siRNA) delivery system in a Rag2 / γc / (RAG-hu) humanized mouse model for HIV-1 infection. HIV-infected humanized Rag2 / γc / mice (RAG-hu) were injected intravenously (i.v.) with dendrimer-siRNA nanoparticles consisting of a cocktail of dicer substrate siRNAs (dsiRNAs) targeting both viral and cellular transcripts. We report in this study that the dendrimer-dsiRNA treatment suppressed HIV-1 infection by several orders of magnitude and protected against viral induced CD4 T-cell depletion. We also demonstrated that follow-up injections of the dendrimer-cocktailed dsiRNAs following viral rebound resulted in complete inhibition of HIV-1 titers. Biodistribution studies demonstrate that the dendrimer-dsiRNAs preferentially accumulate in peripheral blood mononuclear cells (PBMCs) and liver and do not exhibit any discernable toxicity. These data demonstrate for the first time efficacious combinatorial delivery of anti-host and-viral siRNAs for HIV-1 treatment in vivo. The dendrimer delivery approach therefore represents a promising method for systemic delivery of combinations of siRNAs for treatment of HIV-1 infection.
UR - http://www.scopus.com/inward/record.url?scp=82955237641&partnerID=8YFLogxK
U2 - 10.1038/mt.2011.207
DO - 10.1038/mt.2011.207
M3 - Article
AN - SCOPUS:82955237641
SN - 1525-0016
VL - 19
SP - 2228
EP - 2238
JO - Molecular Therapy
JF - Molecular Therapy
IS - 12
ER -
Zhou J, Neff CP, Liu X, Zhang J, Li H, Smith DD et al. Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice. Molecular Therapy. 2011 Dec;19(12):2228-2238. doi: 10.1038/mt.2011.207
