2018
DOI: 10.1016/j.ymthe.2018.09.004
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Development of Targeted siRNA Nanocomplexes to Prevent Fibrosis in Experimental Glaucoma Filtration Surgery

Abstract: RNAi induced by double-stranded small interfering RNA (siRNA) molecules has attracted great attention as a naturally occurring approach to silence gene expression with high specificity. The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway is a master regulator of cytoskeletal gene expression and, thus, represents a promising target to prevent fibrosis. A major hurdle to implementing siRNA therapies is the method of delivery, and we have, thus, optimized lipid-peptide-siRNA (LPR) … Show more

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Cited by 39 publications
(39 citation statements)
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“…Different types of nanoparticles have been developed to regulate ocular wound healing. 35 For topical treatment of skin diseases such as diabetic wounds, psoriasis, inflammatory diseases, and fibrosis, lipid nanoparticles, 36 a cationic star-shaped polymer, 37 spherical nucleic acid-gold nanoparticle conjugates, 38 and mesoporous silica-based nanoparticles 39 have been developed.…”
Section: Discussionmentioning
confidence: 99%
“…Different types of nanoparticles have been developed to regulate ocular wound healing. 35 For topical treatment of skin diseases such as diabetic wounds, psoriasis, inflammatory diseases, and fibrosis, lipid nanoparticles, 36 a cationic star-shaped polymer, 37 spherical nucleic acid-gold nanoparticle conjugates, 38 and mesoporous silica-based nanoparticles 39 have been developed.…”
Section: Discussionmentioning
confidence: 99%
“…In our experiments, we used nanoparticles as a carrier system to deliver the ITCH siRNA in vivo. This was based on our previous findings that the receptor-targeted liposome-peptide-siRNA nanoparticle is an efficient delivery system for ex vivo and in vivo applications [49][50][51][52][53] . The formulation of the nanoparticles contains peptide ME27 which can mediate receptor-specific targeting via its interaction with integrin αvβ3 and αvβ5 on cells.…”
Section: Discussionmentioning
confidence: 99%
“…RNAi to MRTF reduced scarring in the fibrotic "bleb" made during the glaucoma filtration surgery to relieve pressure in the eye. 83,84 Several other gene knockdown strategies for ocular scarring are also being tested in animals. 1,[9][10][11]14 In this study, we used the fully modified siRNA conjugate to achieve maximal activity and longevity of the effect in vivo.…”
Section: Discussionmentioning
confidence: 99%
“…RNAi to MRTF reduced scarring in the fibrotic “bleb” made during the glaucoma filtration surgery to relieve pressure in the eye. 83 , 84 Several other gene knockdown strategies for ocular scarring are also being tested in animals. 1 , 9 , 10 , 11 , 14 …”
Section: Discussionmentioning
confidence: 99%