Abstract

The liver plays a major role in many inherited and acquired genetic disorders. It is also the site for the treatment of certain inborn errors of metabolism that do not directly cause injury to the liver. The advancement of nucleic acid-based therapies for liver maladies has been severely limited because of the myriad untoward side effects and methodological limitations. To address these issues, research efforts in recent years have been intensified toward the development of targeted gene approaches using novel genetic tools, such as zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats as well as various nonviral vectors such as Sleeping Beauty transposons, PiggyBac transposons, and PhiC31 integrase. Although each of these methods uses a distinct mechanism of gene modification, all of them are dependent on the efficient delivery of DNA and RNA molecules into the cell. This review provides an overview of current and emerging therapeutic strategies for liver-targeted gene therapy and gene repair. Liver Transpl 21:718-737, 2015.

Original languageEnglish (US)
Pages (from-to)718-737
Number of pages20
JournalLiver Transplantation
Volume21
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Genetic Therapy
Liver
Clustered Regularly Interspaced Short Palindromic Repeats
Genes
Integrases
Beauty
Inborn Errors Metabolism
Inborn Genetic Diseases
Zinc Fingers
Nucleic Acids
Therapeutics
RNA
DNA
Wounds and Injuries
Research

Cite this

Liver-targeted gene therapy : Approaches and challenges. / Aravalli, Rajagopal N.; Belcher, John D.; Steer, Clifford J.

In: Liver Transplantation, Vol. 21, No. 6, 01.06.2015, p. 718-737.

Research output: Contribution to journalArticle

@article{6ff45c4abc4d4d86b588b62556c408d5,
title = "Liver-targeted gene therapy: Approaches and challenges",
abstract = "The liver plays a major role in many inherited and acquired genetic disorders. It is also the site for the treatment of certain inborn errors of metabolism that do not directly cause injury to the liver. The advancement of nucleic acid-based therapies for liver maladies has been severely limited because of the myriad untoward side effects and methodological limitations. To address these issues, research efforts in recent years have been intensified toward the development of targeted gene approaches using novel genetic tools, such as zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats as well as various nonviral vectors such as Sleeping Beauty transposons, PiggyBac transposons, and PhiC31 integrase. Although each of these methods uses a distinct mechanism of gene modification, all of them are dependent on the efficient delivery of DNA and RNA molecules into the cell. This review provides an overview of current and emerging therapeutic strategies for liver-targeted gene therapy and gene repair. Liver Transpl 21:718-737, 2015.",
author = "Aravalli, {Rajagopal N.} and Belcher, {John D.} and Steer, {Clifford J.}",
year = "2015",
month = "6",
day = "1",
doi = "10.1002/lt.24122",
language = "English (US)",
volume = "21",
pages = "718--737",
journal = "Liver Transplantation",
issn = "1527-6465",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - Liver-targeted gene therapy

T2 - Approaches and challenges

AU - Aravalli, Rajagopal N.

AU - Belcher, John D.

AU - Steer, Clifford J.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - The liver plays a major role in many inherited and acquired genetic disorders. It is also the site for the treatment of certain inborn errors of metabolism that do not directly cause injury to the liver. The advancement of nucleic acid-based therapies for liver maladies has been severely limited because of the myriad untoward side effects and methodological limitations. To address these issues, research efforts in recent years have been intensified toward the development of targeted gene approaches using novel genetic tools, such as zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats as well as various nonviral vectors such as Sleeping Beauty transposons, PiggyBac transposons, and PhiC31 integrase. Although each of these methods uses a distinct mechanism of gene modification, all of them are dependent on the efficient delivery of DNA and RNA molecules into the cell. This review provides an overview of current and emerging therapeutic strategies for liver-targeted gene therapy and gene repair. Liver Transpl 21:718-737, 2015.

AB - The liver plays a major role in many inherited and acquired genetic disorders. It is also the site for the treatment of certain inborn errors of metabolism that do not directly cause injury to the liver. The advancement of nucleic acid-based therapies for liver maladies has been severely limited because of the myriad untoward side effects and methodological limitations. To address these issues, research efforts in recent years have been intensified toward the development of targeted gene approaches using novel genetic tools, such as zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats as well as various nonviral vectors such as Sleeping Beauty transposons, PiggyBac transposons, and PhiC31 integrase. Although each of these methods uses a distinct mechanism of gene modification, all of them are dependent on the efficient delivery of DNA and RNA molecules into the cell. This review provides an overview of current and emerging therapeutic strategies for liver-targeted gene therapy and gene repair. Liver Transpl 21:718-737, 2015.

UR - http://www.scopus.com/inward/record.url?scp=84930016507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930016507&partnerID=8YFLogxK

U2 - 10.1002/lt.24122

DO - 10.1002/lt.24122

M3 - Article

VL - 21

SP - 718

EP - 737

JO - Liver Transplantation

JF - Liver Transplantation

SN - 1527-6465

IS - 6

ER -