Matches in SemOpenAlex for { <https://semopenalex.org/work/W3014113143> ?p ?o ?g. }
- W3014113143 endingPage "5080" @default.
- W3014113143 startingPage "5065" @default.
- W3014113143 abstract "Abstract Disabling hearing loss impacts ∼466 million individuals worldwide with 34 million children affected. Gene and pharmacotherapeutic strategies to rescue auditory function in mouse models of human deafness are most effective when administered before hearing onset, after which therapeutic efficacy is significantly diminished or lost. We hypothesize that preemptive correction of a mutation in the fetal inner ear prior to maturation of the sensory epithelium will optimally restore sensory function. We previously demonstrated that transuterine microinjection of a splice-switching antisense oligonucleotide (ASO) into the amniotic cavity immediately surrounding the embryo on embryonic day 13–13.5 (E13–13.5) corrected pre-mRNA splicing in the juvenile Usher syndrome type 1c (Ush1c) mouse mutant. Here, we show that this strategy only marginally rescues hearing and partially rescues vestibular function. To improve therapeutic outcomes, we microinjected ASO directly into the E12.5 inner ear. A single intra-otic dose of ASO corrects harmonin RNA splicing, restores harmonin protein expression in sensory hair cell bundles, prevents hair cell loss, improves hearing sensitivity, and ameliorates vestibular dysfunction. Improvements in auditory and vestibular function were sustained well into adulthood. Our results demonstrate that an ASO pharmacotherapeutic administered to a developing organ system in utero preemptively corrects pre-mRNA splicing to abrogate the disease phenotype." @default.
- W3014113143 created "2020-04-10" @default.
- W3014113143 creator A5012040066 @default.
- W3014113143 creator A5013283544 @default.
- W3014113143 creator A5023969163 @default.
- W3014113143 creator A5030513267 @default.
- W3014113143 creator A5035701762 @default.
- W3014113143 creator A5041605141 @default.
- W3014113143 creator A5050915545 @default.
- W3014113143 creator A5068155775 @default.
- W3014113143 creator A5073802505 @default.
- W3014113143 creator A5079641105 @default.
- W3014113143 date "2020-04-06" @default.
- W3014113143 modified "2023-10-14" @default.
- W3014113143 title "Fetal antisense oligonucleotide therapy for congenital deafness and vestibular dysfunction" @default.
- W3014113143 cites W1503832746 @default.
- W3014113143 cites W1568121568 @default.
- W3014113143 cites W1861297144 @default.
- W3014113143 cites W1868187718 @default.
- W3014113143 cites W1971238719 @default.
- W3014113143 cites W1975263204 @default.
- W3014113143 cites W1976775780 @default.
- W3014113143 cites W1985567838 @default.
- W3014113143 cites W2000725203 @default.
- W3014113143 cites W2005044406 @default.
- W3014113143 cites W2013496968 @default.
- W3014113143 cites W2013935392 @default.
- W3014113143 cites W2015192222 @default.
- W3014113143 cites W2017527220 @default.
- W3014113143 cites W2018514799 @default.
- W3014113143 cites W2020272459 @default.
- W3014113143 cites W2025395331 @default.
- W3014113143 cites W2027318031 @default.
- W3014113143 cites W2034060287 @default.
- W3014113143 cites W2059424037 @default.
- W3014113143 cites W2068184290 @default.
- W3014113143 cites W2079718713 @default.
- W3014113143 cites W2080703941 @default.
- W3014113143 cites W2081628937 @default.
- W3014113143 cites W2084528861 @default.
- W3014113143 cites W2086528950 @default.
- W3014113143 cites W2090611273 @default.
- W3014113143 cites W2090804804 @default.
- W3014113143 cites W2098102650 @default.
- W3014113143 cites W2099237806 @default.
- W3014113143 cites W2099540110 @default.
- W3014113143 cites W2100706309 @default.
- W3014113143 cites W2100977485 @default.
- W3014113143 cites W2103569060 @default.
- W3014113143 cites W2104453327 @default.
- W3014113143 cites W2115222513 @default.
- W3014113143 cites W2121969023 @default.
- W3014113143 cites W2144287136 @default.
- W3014113143 cites W2146989624 @default.
- W3014113143 cites W2149414920 @default.
- W3014113143 cites W2150691762 @default.
- W3014113143 cites W2156283009 @default.
- W3014113143 cites W2158442258 @default.
- W3014113143 cites W2160277514 @default.
- W3014113143 cites W2162778897 @default.
- W3014113143 cites W2162859992 @default.
- W3014113143 cites W2169279496 @default.
- W3014113143 cites W2195799296 @default.
- W3014113143 cites W2210702367 @default.
- W3014113143 cites W2285838982 @default.
- W3014113143 cites W2301243132 @default.
- W3014113143 cites W2344331730 @default.
- W3014113143 cites W2406962855 @default.
- W3014113143 cites W2520737352 @default.
- W3014113143 cites W2541006501 @default.
- W3014113143 cites W2570201053 @default.
- W3014113143 cites W2580370883 @default.
- W3014113143 cites W2582711285 @default.
- W3014113143 cites W2586573214 @default.
- W3014113143 cites W2606848380 @default.
- W3014113143 cites W2606911774 @default.
- W3014113143 cites W2701861245 @default.
- W3014113143 cites W2746713428 @default.
- W3014113143 cites W2762688646 @default.
- W3014113143 cites W2778806019 @default.
- W3014113143 cites W2800246001 @default.
- W3014113143 cites W2808165867 @default.
- W3014113143 cites W2808202810 @default.
- W3014113143 cites W2809391656 @default.
- W3014113143 cites W2811414439 @default.
- W3014113143 cites W2860078943 @default.
- W3014113143 cites W2883876697 @default.
- W3014113143 cites W2887336438 @default.
- W3014113143 cites W2889424788 @default.
- W3014113143 cites W2895334061 @default.
- W3014113143 cites W2895512177 @default.
- W3014113143 cites W2897295193 @default.
- W3014113143 cites W2902016625 @default.
- W3014113143 cites W2906678048 @default.
- W3014113143 cites W2912572612 @default.
- W3014113143 cites W2915730303 @default.
- W3014113143 cites W2916730093 @default.
- W3014113143 cites W2940301838 @default.