RNA therapeutics for retinal diseases

被引:25
作者
Gemayel, Michael C. [1 ]
Bhatwadekar, Ashay D. [1 ]
Ciulla, Thomas [1 ,2 ,3 ]
机构
[1] Indiana Univ, Dept Ophthalmol, Eugene & Marilyn Glick Eye Inst, Indianapolis, IN 46202 USA
[2] Clearside Biomed Inc, Preclin & Clin Dev, Alpharetta, GA USA
[3] Midwest Eye Inst, Indianapolis, IN USA
基金
美国国家卫生研究院;
关键词
Antisense oligonucleotides; inherited retinal disease; microRNA; noncoding RNA; RNA therapeutics; short hairpin RNA; small-interfering RNA; translational read-through inducing drugs; TRANSLATIONAL READ-THROUGH; CHOROIDAL NEOVASCULARIZATION; ANTISENSE OLIGONUCLEOTIDES; CYTOMEGALOVIRUS RETINITIS; DIABETIC-RETINOPATHY; MACULAR DEGENERATION; DOWN-REGULATION; MICRORNAS; DELIVERY; MECHANISMS;
D O I
10.1080/14712598.2021.1856365
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Introduction In the retina, noncoding RNA (ncRNA) plays an integral role in regulating apoptosis, inflammatory responses, visual perception, and photo-transduction, with altered levels reported in diseased states. Areas covered MicroRNA (miRNA), a class of ncRNA, regulates post-transcription gene expression through the binding of complementary sites of target messenger RNA (mRNA) with resulting translational repression. Small-interfering RNA (siRNA) is a double-stranded RNA (dsRNA) that regulates gene expression, leading to selective silencing of genes through a process called RNA interference (RNAi). Another form of RNAi involves short hairpin RNA (shRNA). In age-related macular degeneration (AMD) and diabetic retinopathy (DR), miRNA has been implicated in the regulation of angiogenesis, oxidative stress, immune response, and inflammation. Expert opinion Many RNA-based therapies in development are conveniently administered intravitreally, with the potential for pan-retinal effect. The majority of these RNA therapeutics are synthetic ncRNA's and hold promise for the treatment of AMD, DR, and inherited retinal diseases (IRDs). These RNA-based therapies include siRNA therapy with its high specificity, shRNA to 'knock down' autosomal dominant toxic gain of function-mutated genes, antisense oligonucleotides (ASOs), which can restore splicing defects, and translational read-through inducing drugs (TRIDs) to increase expression of full-length protein from genes with premature stop codons.
引用
收藏
页码:603 / 613
页数:11
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