title: Induction of Transcriptional Gene Silencing by Expression of shRNA Directed to c-Myc P2 Promoter in Hepatocellular Carcinoma by Tissue-Specific Virosomal Delivery.
abstract: Double-stranded RNA-mediated transcriptional gene silencing (TGS) has shown promising results over posttranscriptional gene silencing (PTGS) due to its long term and heritable nature. Various research groups have shed light on different mechanisms by which TGS operate. Some of these include histone modification, DNA methylation, or restriction of RNA polymerase binding onto the target gene's promoter. This serves as an added advantage since permanent c-Myc inactivation is critical for suppressing hepatocellular carcinoma (HCC). Inability to target cancer cells specifically, without affecting the normal cells, has been one of the biggest drawbacks of an effective cancer therapy. Therefore, we aimed to overcome this barrier by first generating tumor-specific transcriptional units expressing TGS inducing shRNAs against c-Myc's P2 promoter only in neoplastic liver cells. Secondly, we coupled this TGS inducing system with Sendai fusion virosomes for liver-specific delivery to minimize nonspecific side effects in vitro.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India. khalid_aiims@hotmail.com.|International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, 34149, Italy. khalid_aiims@hotmail.com.
authors.forename: Mohammad Khalid
authors.initials: MK
authors.lastname: Zakaria
authors.affiliation: Department of Biochemistry, University of Delhi, South Campus, New Delhi, 110021, India.
authors.forename: Debi P
authors.initials: DP
authors.lastname: Sarkar
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Parthaprasad
authors.initials: P
authors.lastname: Chattopadhyay
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018899:CpG Islands; D019175:DNA Methylation; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D016259:Genes, myc; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D014162:Transfection / Q000379:methods; D022701:Virosomes
chemical_list: D034741:RNA, Small Interfering; D022701:Virosomes
keywords: Transcriptional gene silencing; Virosomal delivery; shRNAs