Category: RNAi Against Receptors

Featured Paper:  "HIV-1 resistance conferred by siRNA cosuppression of CXCR4 and CCR5 coreceptors by a bispecific lentiviral vector."

Authors:  Joseph Anderson and Ramesh Akkina

Year of Publication: 2005

Journal:  AIDS Research and Therapy. Vol. 2:1.

Online Availability:  Full Text at Aids Research and Therapy Journal Website.

Significance

HIV uses various cell surface receptors to enter the cells it infects.  CD4 receptors are involved in the entry process for all types of HIV.  There are two additional receptors involved in the entry process in particular cell types.  M-Tropic HIV additionally use the CCR5 receptor to enter cells, while T-Tropic strains use the CXCR4 receptor [Wikipedia]. 

          This area of RNAi research focuses on selectively downregulating these receptors.  An experiment involving this type of research would usually apply RNAi before the cell is infected with the virus.  If an RNAi therapy comes out of this research, it will be be a mainly preemptive one.  The immunizing process would involve harvesting young immune system cells, injecting them with stably expressed siRNAs, and injecting the cells back into the body.  Theoretically, these cells--that do not express the entry proteins required by HIV--and their descendents will unaffected by the virus.

          The featured experiment stands out because it used a bispecific construct that encoded siRNAs targeting both CCR5 and CXCR4 receptors (siRNAs targeting only one receptor will give the subject immunity to only one type of HIV strain).  Significant viral resistance was observed.