Acute and chronic hepatitis B virus(HBV) infections remain to present a major global health problem. The infection can be associated with acute symptomatic or asymptomatic hepatitis which can cause chronic inflammatio...Acute and chronic hepatitis B virus(HBV) infections remain to present a major global health problem. The infection can be associated with acute symptomatic or asymptomatic hepatitis which can cause chronic inflammation of the liver and over years this can lead to cirrhosis and the development of hepatocellularcarcinomas. Currently available therapeutics for chronically infected individuals aim at reducing viral replication and to slow down or stop the progression of the disease. Therefore, novel treatment options are needed to efficiently combat and eradicate this disease. Here we provide a state of the art overview of gene therapeutic approaches to inhibit HBV replication. We discuss non-viral and viral approaches which were explored to deliver therapeutic nucleic acids aiming at reducing HBV replication. Types of delivered therapeutic nucleic acids which were studied since many years include antisense oligodeoxynucleotides and antisense RNA, ribozymes and DNAzymes, RNA interference, and external guide sequences. More recently designer nucleases gained increased attention and were exploited to destroy the HBV genome. In addition we mention other strategies to reduce HBV replication based on delivery of DNA encoding dominant negative mutants and DNA vaccination. In combination with available cell culture and animal models for HBV infection, in vitro and in vivo studies can be performed to test efficacy of gene therapeutic approaches. Recent progress but also challenges will be specified and future perspectives will be discussed. This is an exciting time to explore such approaches because recent successes of gene therapeutic strategies in the clinic to treat genetic diseases raise hope to find alternative treatment options for patients chronically infected with HBV.展开更多
Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly children.Recently,adenoviruses have garnered significant interest as a versatile tool in ...Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly children.Recently,adenoviruses have garnered significant interest as a versatile tool in gene therapy,tumor treatment,and vaccine vector development.Over the past two decades,the advent of recombineering,a method based on homologous recombination,has notably enhanced the utility of adenoviral vectors in therapeutic applications.This review summarizes recent advancements in the use of human adenoviral vectors in medicine and discusses the pivotal role of recombineering in the development of these vectors.Additionally,it highlights the current achievements and potential future impact of therapeutic adenoviral vectors.展开更多
基金Supported by The Else-Kröner-Fresenius-Foundation(EKFS)and the UWH Forschungsförderung.
文摘Acute and chronic hepatitis B virus(HBV) infections remain to present a major global health problem. The infection can be associated with acute symptomatic or asymptomatic hepatitis which can cause chronic inflammation of the liver and over years this can lead to cirrhosis and the development of hepatocellularcarcinomas. Currently available therapeutics for chronically infected individuals aim at reducing viral replication and to slow down or stop the progression of the disease. Therefore, novel treatment options are needed to efficiently combat and eradicate this disease. Here we provide a state of the art overview of gene therapeutic approaches to inhibit HBV replication. We discuss non-viral and viral approaches which were explored to deliver therapeutic nucleic acids aiming at reducing HBV replication. Types of delivered therapeutic nucleic acids which were studied since many years include antisense oligodeoxynucleotides and antisense RNA, ribozymes and DNAzymes, RNA interference, and external guide sequences. More recently designer nucleases gained increased attention and were exploited to destroy the HBV genome. In addition we mention other strategies to reduce HBV replication based on delivery of DNA encoding dominant negative mutants and DNA vaccination. In combination with available cell culture and animal models for HBV infection, in vitro and in vivo studies can be performed to test efficacy of gene therapeutic approaches. Recent progress but also challenges will be specified and future perspectives will be discussed. This is an exciting time to explore such approaches because recent successes of gene therapeutic strategies in the clinic to treat genetic diseases raise hope to find alternative treatment options for patients chronically infected with HBV.
基金the DFG grant EH 192/5-3(to AE),the internal grant program(project IFF 2024-91)f the Faculty of Health at Witten/Herdecke University(WZ and KS)and the PhD program at Witten/Herdecke University(LK).
文摘Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly children.Recently,adenoviruses have garnered significant interest as a versatile tool in gene therapy,tumor treatment,and vaccine vector development.Over the past two decades,the advent of recombineering,a method based on homologous recombination,has notably enhanced the utility of adenoviral vectors in therapeutic applications.This review summarizes recent advancements in the use of human adenoviral vectors in medicine and discusses the pivotal role of recombineering in the development of these vectors.Additionally,it highlights the current achievements and potential future impact of therapeutic adenoviral vectors.
