Combinational therapy for potential HIV-1 eradication and vaccination.
Eradication of HIV would avert the pandemic high rates of deaths and save the healthcare resources in treatment and prevention costs, however, it is clear that this goal is not achievable with existing anti-HIV drugs due to HIV evolvement in great magnitude and diversity. Despite recent reports of short interfering RNA-directed silencing of HIV gene activities, there remain many challenges in overcoming the complications of HIV mutation in the management of clinical HIV-infected cells. Here we describe a combinational therapy of antiviral deoxynucleotidylated RNA hybrid transfection and interleukin-2 adjuvant treatment that was able to consistently silence 99% mutant type HIV-1 infections of T lymphocytes mediated through a novel post-transcriptional gene silencing mechanism. This combined therapy not only induced strong suppression on mixed type HIV-1 replication but also boosted the immunity and proliferation of normal T lymphocytes. The outgrowth of non-infected T cells resulted in the elimination of 76% HIV-infected cells 1 week after the combinational therapy. These findings promise to provide an immediate therapy in both acute and chronic HIV infections as well as a potential vaccination strategy for AIDS eradication.
Lin
Shi-Lung
SL
Department of Gene Medicine, Epiclone Inc., Alhambra, CA 91801, USA. shilungl@sbcglobal.net
Ying
Shao-Yao
SY
D016915:AIDS Vaccines / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics
D016915:AIDS Vaccines; D007376:Interleukin-2; D012330:RNA, Double-Stranded