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4篇 您的检索式:作者名="Patrick Arbuthnot"
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1Harnessing the RNA interference pathway to advance treatment and prevention of hepatocellular carcinoma显示文摘Primary liver cancer is the fifth most common malignan- cy in the world and is a leading cause of cancer-related mortality.Available treatment for hepatocellular carcino- ma(HCC),the commonest primary liver cancer,is rarely curative and there is a need to develop therapy that is more effective.Specific and powerful gene silencing that can be achieved by activating RNA interference(RNAi) has generated enthusiasm for exploiting this pathway for HCC therapy.Many studies have been carried out with the aim of silencing HCC-related cellular oncogenes or the hepatocarcinogenic hepatitis B virus(HBV)and hepatitis C virus(HCV).Proof of principle studies have demonstrated promising results,and an early clinical trial assessing RNAi-based HBV therapy is currently in progress.Although the data augur well,there are several significant hurdles that need to be overcome before the goal of RNAi-based therapy for HCC is realized.Particu- larly important are the efficient and safe delivery of RNAi effecters to target malignant tissue and the limitation of unintended harmful non-specific effects.Patrick Arbuthnot Liam Jed Thompson 2008World Journal of Gastroenterology2008,14,11:14
2Silencing hepatitis B virus covalently closed circular DNA: The potential of an epigenetic therapy approach显示文摘Global prophylactic vaccination programmes have helped to curb new hepatitis B virus(HBV)infections.However,it is estimated that nearly 300 million people are chronically infected and have a high risk of developing hepatocellular carcinoma.As such,HBV remains a serious health priority and the development of novel curative therapeutics is urgently needed.Chronic HBV infection has been attributed to the persistence of the covalently closed circular DNA(cccDNA)which establishes itself as a minichromosome in the nucleus of hepatocytes.As the viral transcription intermediate,the cccDNA is responsible for producing new virions and perpetuating infection.HBV is dependent on various host factors for cccDNA formation and the minichromosome is amenable to epigenetic modifications.Two HBV proteins,X(HBx)and core(HBc)promote viral replication by modulating the cccDNA epigenome and regulating host cell responses.This includes viral and host gene expression,chromatin remodeling,DNA methylation,the antiviral immune response,apoptosis,and ubiquitination.Elimination of the cccDNA minichromosome would result in a sterilizing cure;however,this may be difficult to achieve.Epigenetic therapies could permanently silence the cccDNA minichromosome and promote a functional cure.This review explores the cccDNA epigenome,how host and viral factors influence transcription,and the recent epigenetic therapies and epigenome engineering approaches that have been described.Prashika Singh Dylan Kairuz Patrick Arbuthnot Kristie Bloom 2021World Journal of Gastroenterology2021,27,23:1
3Inhibition of Hepatitis B Virus Replication by Helper Dependent Adenoviral Vectors Expressing Artificial Anti-HBV Pri-miRs from a Liver-Specific Promoter显示文摘Mohube Betty Mowa Carol Crowther Abdullah Ely Patrick Arbuthnot Ammad Ahmad Farooqi 2014BioMed Research International2014,,:1
4Progress and prospects of engineered sequence-specific DNA modulating technologies for the management of liver diseases显示文摘Liver diseases are one of the leading causes of mortality in the world. The hepatic illnesses, which include inherited metabolic disorders, hemophilias and viralhepatitides, are complex and currently difficult to treat. The maturation of gene therapy has heralded new avenues for developing effective intervention for these diseases. DNA modification using gene therapy is now possible and available technology may be exploited to achieve long term therapeutic benefit. The ability to edit DNA sequences specifically is of paramount importance to advance gene therapy for application to liver diseases. Recent development of technologies that allow for this has resulted in rapid advancement of gene therapy to treat several chronic illnesses. Improvements in application of derivatives of zinc finger proteins(ZFPs), transcription activator-like effectors(TALEs), homing endonucleases(HEs) and clustered regularly interspaced palindromic repeats(CRISPR) and CRISPR associated(Cas) systems have been particularly important. These sequence-specific technologies may be used to modify genes permanently and also to alter gene transcription for therapeutic purposes. This review describes progress in development of ZFPs, TALEs, HEs and CRISPR/Cas for application to treating liver diseases.Samantha A Nicholson Buhle Moyo Patrick B Arbuthnot 2015World Journal of Hepatology2015,7,6:0
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