Abstract
Despite advances and options available in gene therapy for HIV-1 infection, its application in the clinical setting has been challenging. Although published data from HIV-1 clinical trials show safety and proof of principle for gene therapy, positive clinical outcomes for infected patients have yet to be demonstrated. The cause for this slow progress may arise from the fact that HIV is a complex multi-organ system infection. There is uncertainty regarding the types of cells to target by gene therapy and there are issues regarding insufficient transduction of cells and long-term expression. This paper discusses state-of-the-art molecular approaches against HIV-1 and the application of these treatments in current and ongoing clinical trials.
Highlights
Introduction of suicide geneTransdominant negative protein Transdominant negative protein Transdominant negative proteins and anti-sense RNA Transdominant negative proteinTransdominant negative proteinChimeric receptor Chimeric receptor Chimeric receptorRNA decoy Ribozyme RibozymeCTL response cleared modified cells [16].Detected Rev M10 until 2 months post infusion, preferential survival [36].Detected Rev M10 until 6 months post infusion, preferential survival [37].Anti-human immunodeficiency virus (HIV) genes consistently detected for >100 weeks in six of six patients
As reported in the literature, the trials conducted to date have used a suicide gene (HyTK), transdominant negative proteins (Rev M10, transdominant negative mutant Rev protein (TdRev), or huM10), a chimeric receptor (CDζ), an RNA decoy (RRE), and ribozymes
In second patient, detected vector in the progeny for >3 years, remission of leukemia and good viral load control achieved by administering highly active antiretroviral therapy (HAART) that cannot be attributed to gene therapy [38,39]
Summary
In 1983, a new virus was first isolated and associated with acquired immune deficiency syndrome (AIDS) [1]. As an anti-HIV strategy this method was tried in vitro as proof-of-concept in a study that used a retrovirus to transduce autologous CD8+ cells from HIV-infected patients; the suicide gene was thymidine kinase expressed as a fusion protein with hygromycin phosphotransferase [16]. As reported in the literature, the trials conducted to date have used a suicide gene (HyTK), transdominant negative proteins (Rev M10, TdRev, or huM10), a chimeric receptor (CDζ), an RNA decoy (RRE), and ribozymes (anti-tat/vpr ribozyme and tat ribozyme, RRz2). There were no detectable immune responses to the 'foreign proteins' (Rev M10 or MLV gp envelope protein) Though these studies with Rev M10 showed an improved efficacy of gene delivery with a retroviral vector, there was no effect on the patients' viral loads [37]. A 2005 study involving the transdominant negative protein approach was focused on the pediatric age group of
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
