potent inhibition of HIV-1 infection in cultured cells. We will extend our analyses of these constructs to primary CD34+ cells and T-lymphocytes as part of specific aim 1.
In aim 2 further analyses of the functional role of HIV-1 RNA trafficking through the nucleolus will be explored. Specifically, we will investigate the possibility that 2'0-methyl covalent backbone modifications in the R region of HN-1 RNA are guided by a cellular small nucleolar RNA. We will engineer a small nucleolar RNA to misdirect 2'0 methylations to specific sites of protein interaction in the HIV TAR and Rl3E elements. Finally, an in vivo SELEX scheme will be developec to select for new targets, both in HIV-1 and cellular RNAs using a randomized binding arm library of nucleolar localized ribozymes. The results of the work proposed in this aim should extend our knowledge of the functional role of HIV RNA and protein trafficking through tht nucleolus, and provide new ribozymes and other inhibitory RNAs for inhibition of HIV-1 infection. The overall objective of this work is tc enhance our understanding of HIV RNA localization via the use of ribozymes, and to identify the best ribozyme-HIV target strategies for future use in human gene therapy. I

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI029329-23
Application #
8103984
Study Section
Special Emphasis Panel (NSS)
Program Officer
Voulgaropoulou, Frosso
Project Start
1996-07-03
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
23
Fiscal Year
2011
Total Cost
$671,040
Indirect Cost
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
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Zhou, Jiehua; Shum, Ka-To; Burnett, John C et al. (2013) Nanoparticle-Based Delivery of RNAi Therapeutics: Progress and Challenges. Pharmaceuticals (Basel) 6:85-107
Chung, Janet; Zhang, Jane; Li, Haitang et al. (2012) Endogenous MCM7 microRNA cluster as a novel platform to multiplex small interfering and nucleolar RNAs for combinational HIV-1 gene therapy. Hum Gene Ther 23:1200-8

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