Inhibition of Hepatitis B Virus Replication by Helper Dependent Adenoviral Vectors Expressing Artificial Anti-HBV Pri-miRs from a Liver-Specific Promoter
Research on applying RNA interference (RNAi) to counter HBV replication has led to identification of potential therapeutic sequences. However, before clinical application liver-specific expression and efficient delivery of these sequences remain an important objective. We recently reported short-ter...
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| creator | Mowa, Mohube Betty Crowther, Carol Ely, Abdullah Arbuthnot, Patrick |
| description | Research on applying RNA interference (RNAi) to counter HBV replication has led to identification of potential therapeutic sequences. However, before clinical application liver-specific expression and efficient delivery of these sequences remain an important objective. We recently reported short-term inhibition of HBV replication in vivo by using helper dependent adenoviral vectors (HD Ads) expressing anti-HBV sequences from a constitutively active cytomegalovirus (CMV) promoter. To develop the use of liver-specific transcription regulatory elements we investigated the utility of the murine transthyretin (MTTR) promoter for expression of anti-HBV primary microRNAs (pri-miRs). HD Ads containing MTTR promoter effected superior expression of anti-HBV pri-miRs in mice compared to HD Ads containing the CMV promoter. MTTR-containing HD Ads resulted in HBV replication knockdown of up to 94% in mice. HD Ads expressing trimeric anti-HBV pri-miRs silenced HBV replication for 5 weeks. We previously showed that the product of the codelivered lacZ gene induces an immune response, and the duration of HBV silencing in vivo is likely to be attenuated by this effect. Nevertheless, expression of anti-HBV pri-miRs from MTTR promoter is well suited to countering HBV replication and development of HD Ads through attenuation of their immunostimulatory effects should advance their clinical utility. |
| doi_str_mv | 10.1155/2014/718743 |
| format | Article |
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However, before clinical application liver-specific expression and efficient delivery of these sequences remain an important objective. We recently reported short-term inhibition of HBV replication in vivo by using helper dependent adenoviral vectors (HD Ads) expressing anti-HBV sequences from a constitutively active cytomegalovirus (CMV) promoter. To develop the use of liver-specific transcription regulatory elements we investigated the utility of the murine transthyretin (MTTR) promoter for expression of anti-HBV primary microRNAs (pri-miRs). HD Ads containing MTTR promoter effected superior expression of anti-HBV pri-miRs in mice compared to HD Ads containing the CMV promoter. MTTR-containing HD Ads resulted in HBV replication knockdown of up to 94% in mice. HD Ads expressing trimeric anti-HBV pri-miRs silenced HBV replication for 5 weeks. We previously showed that the product of the codelivered lacZ gene induces an immune response, and the duration of HBV silencing in vivo is likely to be attenuated by this effect. Nevertheless, expression of anti-HBV pri-miRs from MTTR promoter is well suited to countering HBV replication and development of HD Ads through attenuation of their immunostimulatory effects should advance their clinical utility.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2014/718743</identifier><identifier>PMID: 25003129</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Puplishing Corporation</publisher><subject>Adenoviridae - genetics ; Animals ; Base Sequence ; Cell Line, Tumor ; Cytomegalovirus ; Cytomegalovirus - genetics ; Efficiency ; Gene expression ; Gene Expression Regulation, Viral ; Gene Silencing ; Genes, Reporter ; Genetic aspects ; Genetic Vectors - metabolism ; Health aspects ; HEK293 Cells ; Helper Viruses - metabolism ; Hepatitis B virus ; Hepatitis B virus - genetics ; Hepatitis B virus - physiology ; Humans ; Infections ; Laboratories ; Liver ; Liver - metabolism ; Mice ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Organ Specificity - genetics ; Plasmids ; Prealbumin - genetics ; Promoter Regions, Genetic ; Recombination, Genetic - genetics ; RNA polymerase ; RNA Polymerase II - metabolism ; Rodents ; Viral infections ; Virus Replication - genetics</subject><ispartof>BioMed research international, 2014-01, Vol.2014 (2014), p.1-12</ispartof><rights>Copyright © 2014 Mohube Betty Mowa et al.</rights><rights>COPYRIGHT 2014 John Wiley & Sons, Inc.</rights><rights>Copyright © 2014 Mohube Betty Mowa et al. Mohube Betty Mowa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2014 Mohube Betty Mowa et al. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-dcff1338dff8ee20a471e992a69a81b033413eab43327a0e648e9b16843368b03</citedby><cites>FETCH-LOGICAL-c527t-dcff1338dff8ee20a471e992a69a81b033413eab43327a0e648e9b16843368b03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066856/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066856/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27907,27908,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25003129$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Farooqi, Ammad Ahmad</contributor><creatorcontrib>Mowa, Mohube Betty</creatorcontrib><creatorcontrib>Crowther, Carol</creatorcontrib><creatorcontrib>Ely, Abdullah</creatorcontrib><creatorcontrib>Arbuthnot, Patrick</creatorcontrib><title>Inhibition of Hepatitis B Virus Replication by Helper Dependent Adenoviral Vectors Expressing Artificial Anti-HBV Pri-miRs from a Liver-Specific Promoter</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Research on applying RNA interference (RNAi) to counter HBV replication has led to identification of potential therapeutic sequences. 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We previously showed that the product of the codelivered lacZ gene induces an immune response, and the duration of HBV silencing in vivo is likely to be attenuated by this effect. Nevertheless, expression of anti-HBV pri-miRs from MTTR promoter is well suited to countering HBV replication and development of HD Ads through attenuation of their immunostimulatory effects should advance their clinical utility.</description><subject>Adenoviridae - genetics</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Cell Line, Tumor</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus - genetics</subject><subject>Efficiency</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Viral</subject><subject>Gene Silencing</subject><subject>Genes, Reporter</subject><subject>Genetic aspects</subject><subject>Genetic Vectors - metabolism</subject><subject>Health aspects</subject><subject>HEK293 Cells</subject><subject>Helper Viruses - metabolism</subject><subject>Hepatitis B virus</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B virus - physiology</subject><subject>Humans</subject><subject>Infections</subject><subject>Laboratories</subject><subject>Liver</subject><subject>Liver - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BioMed research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mowa, Mohube Betty</au><au>Crowther, Carol</au><au>Ely, Abdullah</au><au>Arbuthnot, Patrick</au><au>Farooqi, Ammad Ahmad</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Hepatitis B Virus Replication by Helper Dependent Adenoviral Vectors Expressing Artificial Anti-HBV Pri-miRs from a Liver-Specific Promoter</atitle><jtitle>BioMed research international</jtitle><addtitle>Biomed Res Int</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>2014</volume><issue>2014</issue><spage>1</spage><epage>12</epage><pages>1-12</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>Research on applying RNA interference (RNAi) to counter HBV replication has led to identification of potential therapeutic sequences. However, before clinical application liver-specific expression and efficient delivery of these sequences remain an important objective. We recently reported short-term inhibition of HBV replication in vivo by using helper dependent adenoviral vectors (HD Ads) expressing anti-HBV sequences from a constitutively active cytomegalovirus (CMV) promoter. To develop the use of liver-specific transcription regulatory elements we investigated the utility of the murine transthyretin (MTTR) promoter for expression of anti-HBV primary microRNAs (pri-miRs). HD Ads containing MTTR promoter effected superior expression of anti-HBV pri-miRs in mice compared to HD Ads containing the CMV promoter. MTTR-containing HD Ads resulted in HBV replication knockdown of up to 94% in mice. HD Ads expressing trimeric anti-HBV pri-miRs silenced HBV replication for 5 weeks. We previously showed that the product of the codelivered lacZ gene induces an immune response, and the duration of HBV silencing in vivo is likely to be attenuated by this effect. Nevertheless, expression of anti-HBV pri-miRs from MTTR promoter is well suited to countering HBV replication and development of HD Ads through attenuation of their immunostimulatory effects should advance their clinical utility.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Puplishing Corporation</pub><pmid>25003129</pmid><doi>10.1155/2014/718743</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenoviridae - genetics Animals Base Sequence Cell Line, Tumor Cytomegalovirus Cytomegalovirus - genetics Efficiency Gene expression Gene Expression Regulation, Viral Gene Silencing Genes, Reporter Genetic aspects Genetic Vectors - metabolism Health aspects HEK293 Cells Helper Viruses - metabolism Hepatitis B virus Hepatitis B virus - genetics Hepatitis B virus - physiology Humans Infections Laboratories Liver Liver - metabolism Mice MicroRNAs - genetics MicroRNAs - metabolism Organ Specificity - genetics Plasmids Prealbumin - genetics Promoter Regions, Genetic Recombination, Genetic - genetics RNA polymerase RNA Polymerase II - metabolism Rodents Viral infections Virus Replication - genetics |
| title | Inhibition of Hepatitis B Virus Replication by Helper Dependent Adenoviral Vectors Expressing Artificial Anti-HBV Pri-miRs from a Liver-Specific Promoter |
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