Personalized gene silencing therapeutics for Huntington disease

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Personalized gene silencing therapeutics for Huntington disease. / Kay, C; Skotte, N H; Southwell, A L; Hayden, M R.

In: Clinical Genetics, Vol. 86, No. 1, 07.2014, p. 29-36.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kay, C, Skotte, NH, Southwell, AL & Hayden, MR 2014, 'Personalized gene silencing therapeutics for Huntington disease', Clinical Genetics, vol. 86, no. 1, pp. 29-36. https://doi.org/10.1111/cge.12385

APA

Kay, C., Skotte, N. H., Southwell, A. L., & Hayden, M. R. (2014). Personalized gene silencing therapeutics for Huntington disease. Clinical Genetics, 86(1), 29-36. https://doi.org/10.1111/cge.12385

Vancouver

Kay C, Skotte NH, Southwell AL, Hayden MR. Personalized gene silencing therapeutics for Huntington disease. Clinical Genetics. 2014 Jul;86(1):29-36. https://doi.org/10.1111/cge.12385

Author

Kay, C ; Skotte, N H ; Southwell, A L ; Hayden, M R. / Personalized gene silencing therapeutics for Huntington disease. In: Clinical Genetics. 2014 ; Vol. 86, No. 1. pp. 29-36.

Bibtex

@article{c1f1baa730764c298db88f6800fa700c,
title = "Personalized gene silencing therapeutics for Huntington disease",
abstract = "Gene silencing offers a novel therapeutic strategy for dominant genetic disorders. In specific diseases, selective silencing of only one copy of a gene may be advantageous over non-selective silencing of both copies. Huntington disease (HD) is an autosomal dominant disorder caused by an expanded CAG trinucleotide repeat in the Huntingtin gene (HTT). Silencing both expanded and normal copies of HTT may be therapeutically beneficial, but preservation of normal HTT expression is preferred. Allele-specific methods can selectively silence the mutant HTT transcript by targeting either the expanded CAG repeat or single nucleotide polymorphisms (SNPs) in linkage disequilibrium with the expansion. Both approaches require personalized treatment strategies based on patient genotypes. We compare the prospect of safe treatment of HD by CAG- and SNP-specific silencing approaches and review HD population genetics used to guide target identification in the patient population. Clinical implementation of allele-specific HTT silencing faces challenges common to personalized genetic medicine, requiring novel solutions from clinical scientists and regulatory authorities.",
keywords = "Gene Silencing, Genes, Dominant, Genetic Therapy, Genetics, Population, Humans, Huntington Disease, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Precision Medicine, Trinucleotide Repeat Expansion",
author = "C Kay and Skotte, {N H} and Southwell, {A L} and Hayden, {M R}",
note = "{\textcopyright} 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2014",
month = jul,
doi = "10.1111/cge.12385",
language = "English",
volume = "86",
pages = "29--36",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS

TY - JOUR

T1 - Personalized gene silencing therapeutics for Huntington disease

AU - Kay, C

AU - Skotte, N H

AU - Southwell, A L

AU - Hayden, M R

N1 - © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2014/7

Y1 - 2014/7

N2 - Gene silencing offers a novel therapeutic strategy for dominant genetic disorders. In specific diseases, selective silencing of only one copy of a gene may be advantageous over non-selective silencing of both copies. Huntington disease (HD) is an autosomal dominant disorder caused by an expanded CAG trinucleotide repeat in the Huntingtin gene (HTT). Silencing both expanded and normal copies of HTT may be therapeutically beneficial, but preservation of normal HTT expression is preferred. Allele-specific methods can selectively silence the mutant HTT transcript by targeting either the expanded CAG repeat or single nucleotide polymorphisms (SNPs) in linkage disequilibrium with the expansion. Both approaches require personalized treatment strategies based on patient genotypes. We compare the prospect of safe treatment of HD by CAG- and SNP-specific silencing approaches and review HD population genetics used to guide target identification in the patient population. Clinical implementation of allele-specific HTT silencing faces challenges common to personalized genetic medicine, requiring novel solutions from clinical scientists and regulatory authorities.

AB - Gene silencing offers a novel therapeutic strategy for dominant genetic disorders. In specific diseases, selective silencing of only one copy of a gene may be advantageous over non-selective silencing of both copies. Huntington disease (HD) is an autosomal dominant disorder caused by an expanded CAG trinucleotide repeat in the Huntingtin gene (HTT). Silencing both expanded and normal copies of HTT may be therapeutically beneficial, but preservation of normal HTT expression is preferred. Allele-specific methods can selectively silence the mutant HTT transcript by targeting either the expanded CAG repeat or single nucleotide polymorphisms (SNPs) in linkage disequilibrium with the expansion. Both approaches require personalized treatment strategies based on patient genotypes. We compare the prospect of safe treatment of HD by CAG- and SNP-specific silencing approaches and review HD population genetics used to guide target identification in the patient population. Clinical implementation of allele-specific HTT silencing faces challenges common to personalized genetic medicine, requiring novel solutions from clinical scientists and regulatory authorities.

KW - Gene Silencing

KW - Genes, Dominant

KW - Genetic Therapy

KW - Genetics, Population

KW - Humans

KW - Huntington Disease

KW - Nerve Tissue Proteins

KW - Polymorphism, Single Nucleotide

KW - Precision Medicine

KW - Trinucleotide Repeat Expansion

U2 - 10.1111/cge.12385

DO - 10.1111/cge.12385

M3 - Journal article

C2 - 24646433

VL - 86

SP - 29

EP - 36

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 1

ER -

ID: 153451225