http://hdl.handle.net/10204/889 Mon, 20 May 2013 12:08:54 GMT 2013-05-20T12:08:54Z http://hdl.handle.net/10204/6656 Title: Point mutations associated with HIV-1 drug resistance, evasion of the immune response and AIDS pathogenesis Authors: Khati, M; Millroy, L Abstract: Point mutations within the human immunodeficiency virus-type 1 (HIV-1) genome confer resistance to antiretroviral drugs. The mutations also help the virus to evade the immune system response and influence transmission and progression of the disease, collectively called acquired immune deficiency syndrome (AIDS) pathogenesis. This chapter presents an up-to-date critical review of the literature and provides a synthesis of the current understanding of HIV-1 point mutations in relation to drug resistance, evasion of the immune system and AIDS pathogenesis. First, to prime the reader, the chapter briefly describes organization and function of the HIV-1 genes. It then pinpoints salient point mutations within specific HIV-1 genes associated with resistance to current antiretroviral drugs. In particular, it pays attention to the env gene and its product, the surface envelope (Env) glycoprotein because the Env protein mediates viral entry, tropism and disease progression. Thus the role and frequencies of point mutations within the env gene is related to HIV-1 transmission dynamics and progression to AIDS. The env gene and Env protein are further unpacked to provide a better understanding of the role point mutations within this gene play in helping the virus to evade antibody mediated immune response. Finally, drawing mainly from our recent research work, the chapter proposes an aptamer-based strategy for the design of desirable approaches that can help circumvent HIV-1 point mutations and delay or diminish drug resistance. Description: Copyright: This is an Open Access journal. This journal authorizes the publication of the information herewith contained. Published in InTech, Rijeka, Croatia Thu, 01 Mar 2012 00:00:00 GMT http://hdl.handle.net/10204/6656 2012-03-01T00:00:00Z http://hdl.handle.net/10204/6338 Title: Nucleic Acid Therapy: from humble beginnings a dynamic technology Authors: Millroy, L Abstract: The term “nucleic acid therapy” encompasses a wide range of technologies for the treatment of a range of plant and animal ailments. As the name implies, it makes use of nucleic acid (either DNA or RNA) as a therapeutic agent. There are six branches namely: antisense, ribozymes, RNA/DNA decoys, triplex forming oligonucleotides (TFO), RNA interference (RNAi) and most recently aptamers. These therapies work by modulating gene expression of either endogenous or invading genes. This review will provide a brief history of each of the technologies as well as an insight into the potential way forward. Description: EMBO global exchange lecture course on HIV AIDS, Stellenbosch, 30 January 2011 - 4 February 2011 Tue, 01 Feb 2011 00:00:00 GMT http://hdl.handle.net/10204/6338 2011-02-01T00:00:00Z http://hdl.handle.net/10204/6325 Title: Selection and application of ssDNA aptamers to detect active TB from sputum samples Authors: Rotherham, LS; Maserumule, C; Dheda, K; Theron, J; Khati, M Abstract: Despite the enormous global burden of tuberculosis (TB), conventional approaches to diagnosis continue to rely on tests that have major drawbacks. The improvement of TB diagnostics relies, not only on good biomarkers, but also upon accurate detection methodologies. The 10-kDa culture filtrate protein (CFP-10) and the 6-kDa early secreted antigen target (ESAT-6) are potent T-cell antigens that are recognised by over 70% of TB patients. Aptamers, a novel sensitive and specific class of detection molecules, has hitherto, not been raised to these relatively TB-specific antigens. This preliminary proof-of-concept study suggests that a diagnosis of active TB using anti-CFP-10.ESAT-6 aptamers applied to human sputum samples is feasible. Description: Copyright: 2012 Rotherham et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Mon, 01 Oct 2012 00:00:00 GMT http://hdl.handle.net/10204/6325 2012-10-01T00:00:00Z http://hdl.handle.net/10204/6312 Title: HIV-1 subtype C primary isolates exhibit high sensitivity to an anti-gp120 RNA aptamer Authors: Mufhandu, HT; Alexandre, KB; Gray, ES; Morris, L; Khati, M Abstract: Globally, HIV-1 subtype C is the most prevalent subtype, yet most antiretroviral drugs are developed against subtype B. UCLA1 RNA aptamer, which we previously showed neutralizes HIV-1 subtype C Env-pseudotyped viruses was examined for neutralization of subtype C primary isolates in PBMC and monocyte-derived macrophages (MDM). We also assessed the ability of subtype C to develop resistance to UCLA1 inhibition by propagating the isolates in increasing concentrations of the aptamer. Description: Copyright: 2012 Mufhandu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Sat, 01 Sep 2012 00:00:00 GMT http://hdl.handle.net/10204/6312 2012-09-01T00:00:00Z