title: siRNAs encapsulated in recombinant capsid protein derived from Dengue serotype 2 virus inhibits the four serotypes of the virus and proliferation of cancer cells.
abstract: siRNA delivery potential of the Dengue virus capsid protein in cultured cells was recently reported, but target knockdown potential in the context of specific diseases has not been explored. In this study we have evaluated the utility of the protein as an siRNA carrier for anti Dengue viral and anti cancer applications using cell culture systems. We show that target specific siRNAs delivered using the capsid protein inhibit infection by the four serotypes of Dengue virus and proliferation of two cancer cell lines. Our data confirm the potential of the capsid for anti Dengue viral and anti cancer RNAi applications. In addition, we have optimized a fermentation strategy to improve the yield of Escherichia coli expressed D2C protein since the reported yields of E. coli expressed flaviviral capsid proteins are low.
authors.affiliation: Therapeutic Proteins Molecular Biology Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India. Electronic address: manoj.kumar@relbio.com.
authors.forename: A S Manoj
authors.initials: AS
authors.lastname: Kumar
authors.affiliation: Therapeutic Proteins Molecular Biology Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: G E C Vidyadhar
authors.initials: GE
authors.lastname: Reddy
authors.affiliation: Therapeutic Proteins Molecular Biology Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Rajmane
authors.affiliation: Therapeutic Proteins Molecular Biology Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: Soumya
authors.initials: S
authors.lastname: Nair
authors.affiliation: Therapeutic Proteins Molecular Biology Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: Sangita
authors.initials: S
authors.lastname: Pai Kamath
authors.affiliation: Therapeutic Proteins Molecular Biology Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: Greeshma
authors.initials: G
authors.lastname: Sreejesh
authors.affiliation: Therapeutic Proteins Molecular Biology Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: Khalander
authors.initials: K
authors.lastname: Basha
authors.affiliation: Therapeutic Proteins Molecular Biology Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: Shailaja
authors.initials: S
authors.lastname: Chile
authors.affiliation: Therapeutic Proteins Molecular Biology Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: Kriti
authors.initials: K
authors.lastname: Ray
authors.affiliation: Therapeutic Proteins Process Development Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: Vivant
authors.initials: V
authors.lastname: Nelly
authors.affiliation: Therapeutic Proteins Process Development Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: Nilesh
authors.initials: N
authors.lastname: Khadpe
authors.affiliation: Therapeutic Proteins Process Development Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: Ravishankar
authors.initials: R
authors.lastname: Kasturi
authors.affiliation: Therapeutic Proteins Molecular Biology Group, Dhirubhai Ambani Life Sciences Centre, Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors.forename: Venkata
authors.initials: V
authors.lastname: Ramana
mesh_terms: D000818:Animals; D000956:Antigens, Viral; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D064107:Aurora Kinase B / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003715:Dengue / Q000821:virology; D003716:Dengue Virus / Q000187:drug effects / Q000235:genetics*; D004337:Drug Carriers; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000956:Antigens, Viral; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D036022:Capsid Proteins; D004337:Drug Carriers; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D064107:Aurora Kinase B
keywords: Aurorakinase; Capsid; Dengue; Rho A; siRNA