alexa Engineering Sequence-specific Transcriptional Repressors To Disable Replication Of Hepatitis B Virus
ISSN: 2329-8936

Transcriptomics: Open Access
Open Access

OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations

700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Share This Page

Additional Info

Loading
Loading Please wait..
 

2nd International Conference on Molecular Biology, Nucleic Acids & Molecular Medicine
August 31-September 01, 2017 Philadelphia, USA

Patrick Arbuthnot, Abdullah Ely, Buhle Moyo, Kristie Bloom, Claudio Mussolino and Toni Cathomen
University of the Witwatersrand, South Africa
University Medical Centre Freiburg, Germany
ScientificTracks Abstracts: Transcriptomics
DOI: 10.4172/2329-8936-C1-012
Abstract
Chronic infection with hepatitis B virus (HBV) remains and is an important global health problem. Carriers of the virus are at high risk for cirrhosis and liver cancer. Available treatment only has modest curative efficacy and improved therapy is a priority to prevent the life-threatening complications that accompany the infection. The viral replication intermediate comprising covalently closed circular DNA (cccDNA) exists as a stable mini-chromosome in infected hepatocytes. Licensed treatment has no effect on cccDNA and devising methods based on gene therapy to disable this replication intermediate has considerable potential. Previous work from our laboratory demonstrated effective inhibition of HBV replication and targeted disruption of cccDNA by Transcription Activator-Like Effector Nucleases (TALENs). Although this approach is promising, unintended mutagenesis may occur in chronic carriers because of TALEN activity at HBV sequences that are integrated into the host genome. To circumvent this problem, we have produced repressor TALEs (rTALEs) that were designed to induce transcriptional repression at essential HBV transcriptional regulatory elements: the basic core promoter/enhancer II and preS2 promoter sequences. KRAB-encoding sequences were fused to the N-terminal regions of TALEs contain sequence-specific DNA binding domains derived from the AvrBs4 N1 Xanthomas TALE. Each rTALE was expressed from the CMV promoter and engineered to interact with an HBV-specific 18bp target. The repressors were incorporated into recombinant adenoassociated viral vectors which were used to deliver the antiviral elements. Inhibition of HBV replication was observed in cell culture models of HBV replication and in vivo. No evidence of toxicity was detected and inhibitory effects were sustained over a period of at least 2 months. Collectively these data indicate that rTALEs are effective against HBV and provide an efficient means of disabling HBV cccDNA without causing mutations that result from target DNA cleavage.
Biography

Patrick Arbuthnot is currently a Personal Professor and Director of the Wits/SAMRC Antiviral Gene Therapy Research Unit at the University of the Witwatersrand in South Africa. After graduating with a Medical degree, he has completed his PhD in 1992 then carried out his Post-Doctoral work at Necker Hospital in Paris, France. On returning to South Africa, he established the Antiviral Gene Therapy Research Unit, which has now published widely on HBV infection, liver cancer, HIV-1 infection and developing new methods of treating these diseases. His main research interest is in advancing use of biological and synthetic nanoparticles to carry potentially therapeutic nucleic acids (DNA or RNA) that are capable of permanently disabling HBV.

image PDF   |   image HTML
 

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords