Adeno-Associated Viral Gene Therapy for Inherited Retinal Disease

Tuyen Ong, Mark Pennesi, David G. Birch, Byron L. Lam, Stephen H. Tsang

Research output: Contribution to journalReview article

Abstract

Inherited retinal diseases (IRDs) are a group of rare, heterogenous eye disorders caused by gene mutations that result in degeneration of the retina. There are currently limited treatment options for IRDs; however, retinal gene therapy holds great promise for the treatment of different forms of inherited blindness. One such IRD for which gene therapy has shown positive initial results is choroideremia, a rare, X-linked degenerative disorder of the retina and choroid. Mutation of the CHM gene leads to an absence of functional Rab escort protein 1 (REP1), which causes retinal pigment epithelium cell death and photoreceptor degeneration. The condition presents in childhood as night blindness, followed by progressive constriction of visual fields, generally leading to vision loss in early adulthood and total blindness thereafter. A recently developed adeno-associated virus-2 (AAV2) vector construct encoding REP1 (AAV2-REP1) has been shown to deliver a functional version of the CHM gene into the retinal pigment epithelium and photoreceptor cells. Phase 1 and 2 studies of AAV2-REP1 in patients with choroideremia have produced encouraging results, suggesting that it is possible not only to slow or stop the decline in vision following treatment with AAV2-REP1, but also to improve visual acuity in some patients.

Original languageEnglish (US)
Article number34
JournalPharmaceutical Research
Volume36
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Gene therapy
Retinal Diseases
Viral Genes
Dependovirus
Genetic Therapy
Viruses
Choroideremia
Retinal Pigments
Retinal Pigment Epithelium
Genes
Blindness
Proteins
Retina
Night Blindness
Photoreceptor Cells
Mutation
Vertebrate Photoreceptor Cells
Choroid
Cell death
Visual Fields

Keywords

  • AAV2-REP1
  • choroideremia
  • gene therapy
  • retina

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Adeno-Associated Viral Gene Therapy for Inherited Retinal Disease. / Ong, Tuyen; Pennesi, Mark; Birch, David G.; Lam, Byron L.; Tsang, Stephen H.

In: Pharmaceutical Research, Vol. 36, No. 2, 34, 01.02.2019.

Research output: Contribution to journalReview article

Ong, Tuyen ; Pennesi, Mark ; Birch, David G. ; Lam, Byron L. ; Tsang, Stephen H. / Adeno-Associated Viral Gene Therapy for Inherited Retinal Disease. In: Pharmaceutical Research. 2019 ; Vol. 36, No. 2.
@article{5046aa9dea32445bb6967cf6f7cc1fac,
title = "Adeno-Associated Viral Gene Therapy for Inherited Retinal Disease",
abstract = "Inherited retinal diseases (IRDs) are a group of rare, heterogenous eye disorders caused by gene mutations that result in degeneration of the retina. There are currently limited treatment options for IRDs; however, retinal gene therapy holds great promise for the treatment of different forms of inherited blindness. One such IRD for which gene therapy has shown positive initial results is choroideremia, a rare, X-linked degenerative disorder of the retina and choroid. Mutation of the CHM gene leads to an absence of functional Rab escort protein 1 (REP1), which causes retinal pigment epithelium cell death and photoreceptor degeneration. The condition presents in childhood as night blindness, followed by progressive constriction of visual fields, generally leading to vision loss in early adulthood and total blindness thereafter. A recently developed adeno-associated virus-2 (AAV2) vector construct encoding REP1 (AAV2-REP1) has been shown to deliver a functional version of the CHM gene into the retinal pigment epithelium and photoreceptor cells. Phase 1 and 2 studies of AAV2-REP1 in patients with choroideremia have produced encouraging results, suggesting that it is possible not only to slow or stop the decline in vision following treatment with AAV2-REP1, but also to improve visual acuity in some patients.",
keywords = "AAV2-REP1, choroideremia, gene therapy, retina",
author = "Tuyen Ong and Mark Pennesi and Birch, {David G.} and Lam, {Byron L.} and Tsang, {Stephen H.}",
year = "2019",
month = "2",
day = "1",
doi = "10.1007/s11095-018-2564-5",
language = "English (US)",
volume = "36",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Adeno-Associated Viral Gene Therapy for Inherited Retinal Disease

AU - Ong, Tuyen

AU - Pennesi, Mark

AU - Birch, David G.

AU - Lam, Byron L.

AU - Tsang, Stephen H.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Inherited retinal diseases (IRDs) are a group of rare, heterogenous eye disorders caused by gene mutations that result in degeneration of the retina. There are currently limited treatment options for IRDs; however, retinal gene therapy holds great promise for the treatment of different forms of inherited blindness. One such IRD for which gene therapy has shown positive initial results is choroideremia, a rare, X-linked degenerative disorder of the retina and choroid. Mutation of the CHM gene leads to an absence of functional Rab escort protein 1 (REP1), which causes retinal pigment epithelium cell death and photoreceptor degeneration. The condition presents in childhood as night blindness, followed by progressive constriction of visual fields, generally leading to vision loss in early adulthood and total blindness thereafter. A recently developed adeno-associated virus-2 (AAV2) vector construct encoding REP1 (AAV2-REP1) has been shown to deliver a functional version of the CHM gene into the retinal pigment epithelium and photoreceptor cells. Phase 1 and 2 studies of AAV2-REP1 in patients with choroideremia have produced encouraging results, suggesting that it is possible not only to slow or stop the decline in vision following treatment with AAV2-REP1, but also to improve visual acuity in some patients.

AB - Inherited retinal diseases (IRDs) are a group of rare, heterogenous eye disorders caused by gene mutations that result in degeneration of the retina. There are currently limited treatment options for IRDs; however, retinal gene therapy holds great promise for the treatment of different forms of inherited blindness. One such IRD for which gene therapy has shown positive initial results is choroideremia, a rare, X-linked degenerative disorder of the retina and choroid. Mutation of the CHM gene leads to an absence of functional Rab escort protein 1 (REP1), which causes retinal pigment epithelium cell death and photoreceptor degeneration. The condition presents in childhood as night blindness, followed by progressive constriction of visual fields, generally leading to vision loss in early adulthood and total blindness thereafter. A recently developed adeno-associated virus-2 (AAV2) vector construct encoding REP1 (AAV2-REP1) has been shown to deliver a functional version of the CHM gene into the retinal pigment epithelium and photoreceptor cells. Phase 1 and 2 studies of AAV2-REP1 in patients with choroideremia have produced encouraging results, suggesting that it is possible not only to slow or stop the decline in vision following treatment with AAV2-REP1, but also to improve visual acuity in some patients.

KW - AAV2-REP1

KW - choroideremia

KW - gene therapy

KW - retina

UR - http://www.scopus.com/inward/record.url?scp=85059742226&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059742226&partnerID=8YFLogxK

U2 - 10.1007/s11095-018-2564-5

DO - 10.1007/s11095-018-2564-5

M3 - Review article

VL - 36

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 2

M1 - 34

ER -