RNA therapeutics in ophthalmology - translation to clinical trials

Gupta, Aanchal; Kafetzis, Konstantinos N; Tagalakis, Aristides D.; Yu‐Wai‐Man, Cynthia

doi:10.1016/j.exer.2021.108482

Cited by 28 publications

(21 citation statements)

References 118 publications

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“…The AON QR-1123 aims to restore vision in patients with RHO-associated autosomal dominant retinitis pigmentosa. QR-1123 is an allele-selective AON that targets the P23H mutation in the rhodopsin (RHO) gene to remove mutant transcripts and is currently in phase I/II clinical trials [ 37 ].…”

Section: Targeting Nucleic Acidmentioning

confidence: 99%

“…For example, there are numerous studies on the development of siRNA for the SCAs using various experimental systems, of which siRNA for SCA3/Machado-Joseph disease (MJD) has seen the most extensive effort towards allele-specific gene silencing [ 72 ]. Similarly, there is extensive siRNA-based research in the ophthalmology field with several ongoing clinical trials for disorders such as glaucoma, dry eye syndrome, age-related macular degeneration and diabetic macular oedema [ 37 ].…”

Section: Targeting Nucleic Acidmentioning

confidence: 99%

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RNA-based therapeutics for neurological diseases

Anthony

2022

RNA Biology

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RNA-based therapeutics have entered the mainstream with seemingly limitless possibilities to treat all categories of neurological disease. Here, common RNA-based drug modalities such as antisense oligonucleotides, small interfering RNAs, RNA aptamers, RNA-based vaccines and mRNA drugs are reviewed highlighting their current and potential applications. Rapid progress has been made across rare genetic diseases and neurodegenerative disorders, but safe and effective delivery to the brain remains a significant challenge for many applications. The advent of individualized RNA-based therapies for ultra-rare diseases is discussed against the backdrop of the emergence of this field into more common conditions such as Alzheimer’s disease and ischaemic stroke. There remains significant untapped potential in the use of RNA-based therapeutics for behavioural disorders and tumours of the central nervous system; coupled with the accelerated development expected over the next decade, the true potential of RNA-based therapeutics to transform the therapeutic landscape in neurology remains to be uncovered.

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Section: Targeting Nucleic Acidmentioning

confidence: 99%

Section: Targeting Nucleic Acidmentioning

confidence: 99%

RNA-based therapeutics for neurological diseases

Anthony

2022

RNA Biology

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“… 10 The anterior segment of the eyeball mainly consists of the cornea, conjunctiva, iris, ciliary body, sclera, aqueous humor, and the lens, while the posterior segment mainly includes the vitreous body, retina, choroid, and sclera. 11 The eyeball has a unique anatomical structure called the blood-eye barrier, which makes it difficult to achieve an effective drug concentration. 12 , 13 Due to the lipophilic surface layer of the cornea and the hydrophilic nature of the inner layer, ointments do not have characteristics of being both fat-soluble and water-soluble, which makes it difficult to achieve an effective intraocular concentration after applying topical medications.…”

Section: Structure Of the Eyeball For Drug Deliverymentioning

confidence: 99%

Ten Years of Knowledge of Nano-Carrier Based Drug Delivery Systems in Ophthalmology: Current Evidence, Challenges, and Future Prospective

Zhang¹,

Jiao²,

Niu³

et al. 2021

IJN

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The complex drug delivery barrier in the eye reduces the bioavailability of many drugs, resulting in poor therapeutic effects. It is necessary to investigate new drugs through appropriate delivery routes and vehicles. Nanotechnology has utilized various nano-carriers to develop potential ocular drug delivery techniques that interact with the ocular mucosa, prolong the retention time of drugs in the eye, and increase permeability. Additionally, nano-carriers such as liposomes, nanoparticles, nano-suspensions, nano-micelles, and nano-emulsions have grown in popularity as an effective theranostic application to combat different microbial superbugs. In this review, we summarize the nano-carrier based drug delivery system developments over the last decade, particularly review the biology, methodology, approaches, and clinical applications of nano-carrier based drug delivery system in the field of ocular therapeutics. Furthermore, this review addresses upcoming challenges, and provides an outlook on potential future trends of nano-carrier-based drug delivery approaches in ophthalmology, and hopes to eventually provide successful applications for treating ocular diseases.

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“…In this study, which is currently on Phase II/III, the intravitreally injected splice-modulating oligo was well tolerated and improved visual acuity in patients [ 49 ]. This breakthrough shows the promise of oligos in eye disorders [ 50 ].…”

Section: Enabling Technologies For Oligonucleotide Therapeuticsmentioning

confidence: 99%

From Antisense RNA to RNA Modification: Therapeutic Potential of RNA-Based Technologies

Adachi

Hengesbach

et al. 2021

Biomedicines

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Therapeutic oligonucleotides interact with a target RNA via Watson-Crick complementarity, affecting RNA-processing reactions such as mRNA degradation, pre-mRNA splicing, or mRNA translation. Since they were proposed decades ago, several have been approved for clinical use to correct genetic mutations. Three types of mechanisms of action (MoA) have emerged: RNase H-dependent degradation of mRNA directed by short chimeric antisense oligonucleotides (gapmers), correction of splicing defects via splice-modulation oligonucleotides, and interference of gene expression via short interfering RNAs (siRNAs). These antisense-based mechanisms can tackle several genetic disorders in a gene-specific manner, primarily by gene downregulation (gapmers and siRNAs) or splicing defects correction (exon-skipping oligos). Still, the challenge remains for the repair at the single-nucleotide level. The emerging field of epitranscriptomics and RNA modifications shows the enormous possibilities for recoding the transcriptome and repairing genetic mutations with high specificity while harnessing endogenously expressed RNA processing machinery. Some of these techniques have been proposed as alternatives to CRISPR-based technologies, where the exogenous gene-editing machinery needs to be delivered and expressed in the human cells to generate permanent (DNA) changes with unknown consequences. Here, we review the current FDA-approved antisense MoA (emphasizing some enabling technologies that contributed to their success) and three novel modalities based on post-transcriptional RNA modifications with therapeutic potential, including ADAR (Adenosine deaminases acting on RNA)-mediated RNA editing, targeted pseudouridylation, and 2′-O-methylation.

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RNA therapeutics in ophthalmology - translation to clinical trials

Cited by 28 publications

References 118 publications

RNA-based therapeutics for neurological diseases

RNA-based therapeutics for neurological diseases

Ten Years of Knowledge of Nano-Carrier Based Drug Delivery Systems in Ophthalmology: Current Evidence, Challenges, and Future Prospective

From Antisense RNA to RNA Modification: Therapeutic Potential of RNA-Based Technologies

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