Module 3: our.topic.here
A short description of our topic
Brief Project Overview
We wish to knock down the viral activities of HIV in mammalian cells by using siRNA to inhibit HIV proliferation. In order to localize and specify only certain cells, in our case gametes, we wish to incorporate the siRNA into a lentivirus and allowing that lentivirus that do not have any harmful DNA or RNA sequences to attack only certain types of cells.
Background
Previous research has shown that HIV proliferation was successfully inhibited by siRNA.
John Capodici, Katalin Karikó and Drew Weissman. Inhibition of HIV-1 Infection by Small Interfering RNA-Mediated RNA Interference <http://www.jimmunol.org/cgi/content/abstract/169/9/5196>
It has also been shown that by using lentiviruses to target specific cellular coat proteins, siRNA can be introduced into only those cells that have been infected by HIV cells, and thus express the coat proteins associated with HIV. CCR5 is a co-receptor that is vital for the infection of HIV viruses. By modifying the lentivirus to recognize CCR5, siRNA designed to inhibit HIV proliferation was introduced into the cells and thus control HIV propagation.
Xiao-Feng Qin, Dong Sung An, Irvin S. Y. Chen, and David Baltimore. Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5 <http://www.pnas.org/cgi/content/abstract/100/1/183>
Project Goal
We wish to target CCR5 and perhaps also CXCR4 expressed by undifferentiated gametes assuming they are infected by HIV. By introducing siRNA that can knock down, or perhaps even knock out the HIV, the gametes will not transmit the HIV into the zygote, and thus hopefully produce an offspring that will not have HIV. This would also be combined with HIV inhibition in human T cells to minimize possibility of HIV transmission through the maternal-fetus placental interactions.
Sources
Miguel Angel Martínez, Bonaventura Clotet and José A. Esté. RNA interference of HIV replication http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W7H-47187D5-1&_user=501045&_coverDate=12%2F01%2F2002&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000022659&_version=1&_urlVersion=0&_userid=501045&md5=d19e8ac4ef0ed43ac644169e32e6c6a0
Martinez, Miguel A a; Gutierrez, Arantxa a; Armand-Ugon, Mercedes a; Blanco, Julia a; Parera, Mariona a; Gomez, Jordi b; Clotet, Bonaventura a; Este, Jose A a. Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication <http://www.aidsonline.com/pt/re/aids/abstract.00002030-200212060-00002.htm;jsessionid=H9FK3pvhMN8x7hw2bG8xF1GsJ19JtFwBB21f4yQJM0GF2TYwTbGz!1600246195!181195629!8091!-1>
Carl D. Novina, Michael F. Murray, Derek M. Dykxhoorn, Paul J. Beresford, Jonathan Riess, Sang-Kyung Lee, Ronald G. Collman, Judy Lieberman, Premlata Shankar & Phillip A. Sharp. siRNA-directed inhibition of HIV-1 infection <http://www.nature.com/nm/journal/v8/n7/abs/nm725.html>
Xiao-Feng Qin, Dong Sung An, Irvin S. Y. Chen, and David Baltimore. Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5 <http://www.pnas.org/cgi/content/abstract/100/1/183>
John Capodici, Katalin Karikó and Drew Weissman. Inhibition of HIV-1 Infection by Small Interfering RNA-Mediated RNA Interference <http://www.jimmunol.org/cgi/content/abstract/169/9/5196>
Project Details
Please see the Project Details Page
