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Table 1 Current therapies, clinical trials, and strategies to combat HIV

From: RNA interference approaches for treatment of HIV-1 infection

Therapeutic approach Company/institute Component(s) Target(s) Delivery Progress NCT identifier Reference(s)
Combinatorial anti-retroviral therapy (cART) Gilead, Merck, GSK, Pfizer, Tibotec, Abbott, Bristol-Meyers Squibb, Hoffman-La Roche 1. CCR5 antagonist 1. Receptor binding In vivo drug administration Current method to treat HIV   [159]
   2. Fusion inhibitors 2. Membrane fusion     
   3. Nucleoside analogs or RT inhibitors 3. Reverse transcription     
   4. Strand transfer inhibitor 4. Integration     
   5. Protease inhibitors 5. Protein processing     
Peptide or protein vaccines VaxGen, Merck, NIH/NIAID Gp120 Viral envelope In vivo injection Phase I/II/III NCT00001031 [160162]
   Gp41/160     NCT00002402  
   Gag/pol/nef Viral proteins    NCT00223080  
       NCT01435135  
       NCT00002441  
Inhibitory peptide University Medical Center Hamburg-Eppendorf C46 anti-viral peptide Viral fusion to cell membrane Ex vivo retroviral modified CD4+ cells Phase I   [163]
Drug shRNA peptide Calimmune/Caltech/UCLA 1. Bisulfide 1. Transplant conditioning Ex vivo lentiviral modified CD34+ and CD4+ cells Phase I/II NCT01734850 [139]
   2. CCR5 shRNA 2. Host co-receptor     
   3. C46 peptide 3. Viral envelope     
shRNA ribozyme RNA decoy Benitec/City of Hope 1. tat/rev shRNA 1. Viral mRNA Ex vivo lentiviral modified CD34+ cells Phase I NCT00569985 [38, 39]
   2. CCR5 ribozyme 2. Host co-receptor     
   3. TAR decoy 3. Viral Tat protein     
Zinc finger nuclease Sangamo Biosciences 1. CCR5 zinc finger nuclease CCR5 DNA Ex vivo AAV modified autologous CD4+ T cells Phase I-II NCT00842634 [20]
       NCT01044654  
       NCT01543152  
       NCT02225665  
Ribozyme Janssen-Cilag Pty Ltd, UCLA tat-vpr anti-HIV ribozyme Tat-vpr mRNA Ex vivo retroviral modified autologous CD34+ HPC Phase I/II NCT00074997 [40, 41]
       NCT01177059  
Ribozyme UCSD CCR5 ribozyme CCR5 mRNA Ex vivo retroviral modified autologous CD4+ T cells Phase I FDA BB-IND 6405 [42]
Ribozyme Johnson & Johnson, St Vincent’s Hospital Tat anti-HIV ribozyme Translation initiation mRNA of Tat Ex vivo retroviral modified syngeneic CD4+ T cells Phase I NCT00074997 [43]
Ribozyme Ribozyme, City of Hope Tat anti-HIV ribozyme Tat-rev mRNA Ex vivo retroviral modified CD34+ HPC Phase II NCT00002221 [164]
Antisense VIRxSYS Corporation 937 base antisense gene Env mRNA Ex vivo lentiviral (LTR HIV) modified CD4+ cells Phase I/II NCT00131560 [165]
Antisense Enzo Biochem U1/HIV anti-sense RNA (61–68 bases) TAR, tat/rev Ex vivo retroviral modified CD34+ HPC Phase I/II NCT00003942 [166]
       NCT00001535  
RNA decoy Children’s Hospital Los Angeles Rev response element decoy Rev protein Ex vivo retroviral modified CD34+ HPC Phase 0- pilot   [167]
  1. Abbreviations: AAV, adeno-associated virus; HPC, human progenitor cells; LTR, long terminal repeat; NCT, National Clinical Trial; NIH/NIAID, National Institutes of Health/National Institute of Allergy and Infectious Diseases; RT, reverse transcriptase; shRNA, short hairpin RNA