Gene therapy for RPE65-mediated inherited retinal dystrophy completes phase 3

  title={Gene therapy for RPE65-mediated inherited retinal dystrophy completes phase 3},
  author={Helena Lee and Andrew John Lotery},
  journal={The Lancet},
9 Citations

Small Molecule Modifications Significantly Increase the Transfection Efficiency of Low-Molecular Polymer.

The PEI-ER non-viral vector was developed by adding an endoplasmic reticulum (ER) targeting ligand to low molecular weight PEI 1.8K, and this small molecule modifications dramatically improved PEI transfection efficiency while barely interfering with compatibility.

RPE65 mutation frequency and phenotypic variation according to exome sequencing in a tertiary centre for genetic eye diseases in China

Evaluated the frequency of RPE65 mutations and the associated phenotypes based on exome sequencing for Leber congenital amaurosis cases caused by R PE65 mutations.

Retinal Gene Distribution and Functionality Implicated in Inherited Retinal Degenerations Can Reveal Disease-Relevant Pathways for Pharmacologic Intervention

It is reported that, despite the genetic heterogeneity of retinal diseases, potential functional pathways can be elucidated for therapeutic targeting and be used for predictive phenotypic and genotypic modeling of novel IRD presentations.

Polarized AAVR expression determines infectivity by AAV gene therapy vectors

The data suggest the absence of apical AAVR is rate limiting for AAV2, and efficient transduction by A AV2.5T is accomplished using an AAV R independent pathway, and the findings inform the development of gene therapy for CF, and AAV vectors in general.

Adeno-associated Virus Vectors in Gene Therapy

This chapter will review this aspect of AAV-host cellular interactions and outline current developments in generating improved AAV vector systems for human gene therapy applications.

Managing Bardet–Biedl Syndrome—Now and in the Future

Novel interventions are developing at a rapid pace and are explored in this review including genetic therapeutics such as gene therapy, exon skipping therapy, nonsense suppression therapy, and gene editing and other non-genetic therapies such as Gene repurposing, targeted therapies, and non-pharmacological interventions are also discussed.



Gene Therapy for Leber's Congenital Amaurosis is Safe and Effective Through 1.5 Years After Vector Administration

The safety of the intervention and the stability of the improvement in visual and retinal function in these subjects support the use of AAV-mediated gene augmentation therapy for treatment of inherited retinal diseases.

Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial.

A recombinant adeno-associated virus serotype 2 vector, altered to carry the human RPE65 gene (rAAV2-CBSB-hRPE65) restored vision in animal models with R PE65 deficiency, and Comparisons are drawn between the present work and two other studies of ocular gene therapy for RPE 65-LCA that were carried out contemporaneously and reported.

Effect of gene therapy on visual function in Leber's congenital amaurosis.

Three young adult patients with early-onset, severe retinal dystrophy were administered subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human R PE65 promoter.

Safety and efficacy of gene transfer for Leber's congenital amaurosis.

This study investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) and found three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2.

Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement

It is shown that gene therapy improves vision for at least 3 y, but photoreceptor degeneration progresses unabated in humans, and in the canine model, the same result occurs when treatment is at the disease stage equivalent to humans.