Molecular Targeting of Human Papilloma virus oncogene expression using RNA interference Technology

Cervical cancer is the second most common cancer in women throughout the world. Human Papilloma Virus (HPV) infection is the most important risk factor for cervical intraepithelial neoplasia and invasive cervical cancer [1,2, 3]. Cervical cancer occurs early during the productive period of a woman’s life. HPV serotypes 16 and 18 account for nearly 76.7% cervical cancer. Other factors like high parity, early initiation of sexual intercourse, multiple sex partners, low socioeconomic status, poor hygiene etc. have been found to be associated with progression from HPV infection to pathological consequences of cancer. [4]. Physical ablation of HPV induced lesions like cryo therapy, photo therapy, laser cone biopsy and localized radiotherapy are effective to some extent in treating lesions. Removal of afflicted tissue is accomplished by removal of keratinocytes harboring HPV. These are the conventional approaches for treatment of cervical cancer. Prophylactic vaccines are available and should be administered prior to viral exposure. Initiatives for vaccination have been undertaken by the governments and also non- governmental agencies. Attempts are being made to develop therapeutic vaccines that would treat prevailing HPV infection. Use of immunomodulators like interferon and imiquimod induce cytokine production to increase host immune response against HPV infection [5]. Many antioxidants and poly herbal formulations are also in use. Molecular targeting of HPV gene expression using RNA interference technology includes use of antisense oligonucleotides, ribozymes, short interfering RNAs (siRNA), short hairpin RNA (shRNA) etc. The present review is a critique of RNAi approaches used for prevention of cervical cancer. RNA interference (RNAi) occurs naturally in mammalian cells, through which expression of a particular gene can be knocked down with high specificity and selectivity [6]. Pre- clinical studies confirm that RNAi techniques can be used to silence cancer related targets [7]. In vivo studies have also shown favorable outcomes by RNAi targeting of components critical for tumor cell growth, metastasis, angiogenesis and chemo resistance.

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