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Gene therapy for ocular diseases.

ABSTRACT: The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

SUBMITTER: Liu MM

PROVIDER: S-EPMC3154727 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Gene therapy for ocular diseases.

Liu Melissa M MM Tuo Jingsheng J Chan Chi-Chao CC

The British journal of ophthalmology 20100823 5

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapi ...[more]

PMID: 20733027

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Project description:ObjectivesLipid nanoparticles, as a nucleic acid delivery system, have been used as an alternative to treat ocular diseases, since they can cross the ocular barrier and efficiently transfecting nucleic acids to various cells of the eye. The size influences the transfection of genes, biological distribution, diffusion, and cellular uptake. It is therefore important to establish a relationship between size, formulation, and encapsulation percentage.Evidence acquisitionIn this review, we used a search strategy to compare studies of nanomedicine systems aimed at eye diseases where the size of the nanoparticles and the efficiency of encapsulation of genetic material are reported based on the criteria of Preferred Reporting Items for Systematic Reviews (PRISMA ScR 2020 guidelines).ResultsOut of the initial 5932, 169 studies met the inclusion criteria and were included to form the basis of the analysis. Nanoparticles reported are composed mainly of PEG-modified lipids, cholesterol, and cationic lipids, that in combination with messenger or interference RNA, allow the formulation of a nanoparticle with an encapsulation efficiency greater than 95%. The diseases treated mainly focus on conditions related to the retina and cornea. Certain characteristics of nanoparticles increase encapsulation efficiency, such as the size of the nanoparticle and the charge of the outer layer of the nanoparticle.ConclusionIt is still unknown what characteristics lipid nanoparticles should have to successfully treat human eye illnesses. The in vitro and in vivo investigations covered in this review, however, present encouraging results. To improve encapsulation effectiveness and disease gene silencing, nanoparticle formulation is essential. The most stable nanoparticles are those made mostly of cationic lipids, PEG lipids, and cholesterol, which also effectively encapsulate RNA. The encapsulation efficiency is not only influenced by size, but also by other factors such as methods of preparation.

Project description:IntroductionVoretigene neparvovec-rzyl (Luxturna) was approved by the Australian Therapeutic Goods Administration on 4 August 2020 for the treatment of biallelic mutations in the RPE65 gene, a rare cause of congenital and adult-onset retinal dystrophy (predominantly Leber congenital amaurosis). Previous studies have shown that individuals who might participate in gene therapy trials overestimate clinical effect and underestimate risks. However, little is known about the perspectives of patients who may be offered approved gene therapy treatment for ocular conditions (as distinct from participating in clinical trials of gene therapy). The main objective of this study is to develop a tool to assess knowledge, attitudes and perceptions of approved and future genetic therapies among potential recipients of ocular gene therapy. In addition, we aim to assess the quality of life, attitudes towards clinical trials and vision-related quality of life among this cohort.Methods and analysisA new 'Attitudes to Gene Therapy for the Eye' tool will be developed following consultation with people with inherited retinal disease (IRD) and content matter experts. Australians with IRD or their guardians will be asked to complete an internet-based survey comprising existing quality of life and visual function instruments and items for the newly proposed tool. We expect to recruit 500 survey participants from patient support groups, the practices of Australian ophthalmologists who are specialists in IRD and Australian ophthalmic research institutions. Launch is anticipated early 2021. Responses will be analysed using item response theory methodology.Ethics and disseminationThis study has received ethics approval from the University of Melbourne (#2057534). The results of the study will be published in a peer-reviewed journal and will be presented at relevant conferences. Organisations involved in recruitment, and the Patient Engagement Advisory committee will assist the research team with dissemination of the study outcomes.

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Gene therapy for ocular diseases.

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Gene therapy for ocular diseases.

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