Skip to main content

AAV Gene Therapy for MPS1-associated Corneal Blindness.

Publication ,  Journal Article
Vance, M; Llanga, T; Bennett, W; Woodard, K; Murlidharan, G; Chungfat, N; Asokan, A; Gilger, B; Kurtzberg, J; Samulski, RJ; Hirsch, ML
Published in: Sci Rep
February 22, 2016

Although cord blood transplantation has significantly extended the lifespan of mucopolysaccharidosis type 1 (MPS1) patients, over 95% manifest cornea clouding with about 50% progressing to blindness. As corneal transplants are met with high rejection rates in MPS1 children, there remains no treatment to prevent blindness or restore vision in MPS1 children. Since MPS1 is caused by mutations in idua, which encodes alpha-L-iduronidase, a gene addition strategy to prevent, and potentially reverse, MPS1-associated corneal blindness was investigated. Initially, a codon optimized idua cDNA expression cassette (opt-IDUA) was validated for IDUA production and function following adeno-associated virus (AAV) vector transduction of MPS1 patient fibroblasts. Then, an AAV serotype evaluation in human cornea explants identified an AAV8 and 9 chimeric capsid (8G9) as most efficient for transduction. AAV8G9-opt-IDUA administered to human corneas via intrastromal injection demonstrated widespread transduction, which included cells that naturally produce IDUA, and resulted in a >10-fold supraphysiological increase in IDUA activity. No significant apoptosis related to AAV vectors or IDUA was observed under any conditions in both human corneas and MPS1 patient fibroblasts. The collective preclinical data demonstrate safe and efficient IDUA delivery to human corneas, which may prevent and potentially reverse MPS1-associated cornea blindness.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

February 22, 2016

Volume

6

Start / End Page

22131

Location

England

Related Subject Headings

  • Transfection
  • Organ Culture Techniques
  • Mucopolysaccharidosis I
  • Microscopy, Confocal
  • Iduronidase
  • Humans
  • HEK293 Cells
  • Green Fluorescent Proteins
  • Genetic Vectors
  • Genetic Therapy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Vance, M., Llanga, T., Bennett, W., Woodard, K., Murlidharan, G., Chungfat, N., … Hirsch, M. L. (2016). AAV Gene Therapy for MPS1-associated Corneal Blindness. Sci Rep, 6, 22131. https://doi.org/10.1038/srep22131
Vance, Melisa, Telmo Llanga, Will Bennett, Kenton Woodard, Giridhar Murlidharan, Neil Chungfat, Aravind Asokan, et al. “AAV Gene Therapy for MPS1-associated Corneal Blindness.Sci Rep 6 (February 22, 2016): 22131. https://doi.org/10.1038/srep22131.
Vance M, Llanga T, Bennett W, Woodard K, Murlidharan G, Chungfat N, et al. AAV Gene Therapy for MPS1-associated Corneal Blindness. Sci Rep. 2016 Feb 22;6:22131.
Vance, Melisa, et al. “AAV Gene Therapy for MPS1-associated Corneal Blindness.Sci Rep, vol. 6, Feb. 2016, p. 22131. Pubmed, doi:10.1038/srep22131.
Vance M, Llanga T, Bennett W, Woodard K, Murlidharan G, Chungfat N, Asokan A, Gilger B, Kurtzberg J, Samulski RJ, Hirsch ML. AAV Gene Therapy for MPS1-associated Corneal Blindness. Sci Rep. 2016 Feb 22;6:22131.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

February 22, 2016

Volume

6

Start / End Page

22131

Location

England

Related Subject Headings

  • Transfection
  • Organ Culture Techniques
  • Mucopolysaccharidosis I
  • Microscopy, Confocal
  • Iduronidase
  • Humans
  • HEK293 Cells
  • Green Fluorescent Proteins
  • Genetic Vectors
  • Genetic Therapy