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• W2077332675 endingPage "e21352" @default.
• W2077332675 startingPage "e21352" @default.
• W2077332675 abstract "Since RNA interference (RNAi) has the potential to discriminate between single nucleotide changes, there is growing interest in the use of RNAi as a promising therapeutical approach to target dominant disease-associated alleles. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been linked to dominantly inherited Parkinson's disease (PD). We focused on three LRRK2 mutations (R1441G/C and the more prevalent G2109S) hoping to identify shRNAs that would both recognize and efficiently silence the mutated alleles preferentially over the wild-type alleles. Using a luciferase-based reporter system, we identified shRNAs that were able to specifically target the R1441G and R1441C alleles with 80% silencing efficiency. The same shRNAs were able to silence specifically mRNAs encoding either partial or full-length mutant LRRK2 fusion proteins, while having a minimal effect on endogenous wild-type LRRK2 expression when transfected in 293FT cells. Shifting of the mutant recognition site (MRS) from position 11 to other sites (4 and 16, within the 19-mer window of our shRNA design) reduced specificity and overall silencing efficiency. Developing an allele-specific RNAi of G2019S was problematic. Placement of the MRS at position 10 resulted in efficient silencing of reporters (75–80%), but failed to discriminate between mutant and wild-type alleles. Shifting of the MRS to positions 4, 5, 15, 16 increased the specificity of the shRNAs, but reduced the overall silencing efficiency. Consistent with previous reports, these data confirm that MRS placement influences both allele-specificity and silencing strength of shRNAs, while further modification to hairpin design or MRS position may lead to the development of effective G2019S shRNAs. In summary, the effective shRNA against LRRK2 R1441 alleles described herein suggests that RNAi-based therapy of inherited Parkinson's disease is a viable approach towards developing effective therapeutic interventions for this serious neurodegenerative disease." @default.
• W2077332675 created "2016-06-24" @default.
• W2077332675 creator A5016837398 @default.
• W2077332675 creator A5061695954 @default.
• W2077332675 creator A5074486047 @default.
• W2077332675 date "2011-06-21" @default.
• W2077332675 modified "2023-10-18" @default.
• W2077332675 title "Efficient Allele-Specific Targeting of LRRK2 R1441 Mutations Mediated by RNAi" @default.
• W2077332675 cites W113246021 @default.
• W2077332675 cites W1585973412 @default.
• W2077332675 cites W1965850853 @default.
• W2077332675 cites W1966180593 @default.
• W2077332675 cites W1967214356 @default.
• W2077332675 cites W1970848642 @default.
• W2077332675 cites W1971064755 @default.
• W2077332675 cites W1971529004 @default.
• W2077332675 cites W1972088609 @default.
• W2077332675 cites W1973649320 @default.
• W2077332675 cites W1976060898 @default.
• W2077332675 cites W1976268989 @default.
• W2077332675 cites W1978419085 @default.
• W2077332675 cites W1979837223 @default.
• W2077332675 cites W1988142389 @default.
• W2077332675 cites W1990478641 @default.
• W2077332675 cites W1991884446 @default.
• W2077332675 cites W1992365739 @default.
• W2077332675 cites W1992483894 @default.
• W2077332675 cites W1997163042 @default.
• W2077332675 cites W2003883601 @default.
• W2077332675 cites W2006875797 @default.
• W2077332675 cites W2010791234 @default.
• W2077332675 cites W2015419750 @default.
• W2077332675 cites W2017180332 @default.
• W2077332675 cites W2017285096 @default.
• W2077332675 cites W2017906219 @default.
• W2077332675 cites W2027254060 @default.
• W2077332675 cites W2028171714 @default.
• W2077332675 cites W2031884668 @default.
• W2077332675 cites W2032206743 @default.
• W2077332675 cites W2034849392 @default.
• W2077332675 cites W2035943396 @default.
• W2077332675 cites W2038354221 @default.
• W2077332675 cites W2042062646 @default.
• W2077332675 cites W2042237947 @default.
• W2077332675 cites W2042739691 @default.
• W2077332675 cites W2050902269 @default.
• W2077332675 cites W2051587165 @default.
• W2077332675 cites W2063127941 @default.
• W2077332675 cites W2065267787 @default.
• W2077332675 cites W2066296867 @default.
• W2077332675 cites W2072216745 @default.
• W2077332675 cites W2076367135 @default.
• W2077332675 cites W2080679736 @default.
• W2077332675 cites W2089115715 @default.
• W2077332675 cites W2100300726 @default.
• W2077332675 cites W2100894616 @default.
• W2077332675 cites W2101722758 @default.
• W2077332675 cites W2104979554 @default.
• W2077332675 cites W2105381209 @default.
• W2077332675 cites W2106006107 @default.
• W2077332675 cites W2107508122 @default.
• W2077332675 cites W2110157421 @default.
• W2077332675 cites W2113282929 @default.
• W2077332675 cites W2115282717 @default.
• W2077332675 cites W2120262230 @default.
• W2077332675 cites W2124654811 @default.
• W2077332675 cites W2124738784 @default.
• W2077332675 cites W2132354121 @default.
• W2077332675 cites W2133898735 @default.
• W2077332675 cites W2136216054 @default.
• W2077332675 cites W2137901394 @default.
• W2077332675 cites W2151488213 @default.
• W2077332675 cites W2155842589 @default.
• W2077332675 cites W2157645703 @default.
• W2077332675 cites W2159300982 @default.
• W2077332675 cites W2160151905 @default.
• W2077332675 cites W2161239543 @default.
• W2077332675 cites W2161241864 @default.
• W2077332675 cites W2398741430 @default.
• W2077332675 cites W76054165 @default.
• W2077332675 doi "https://doi.org/10.1371/journal.pone.0021352" @default.
• W2077332675 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3119704" @default.
• W2077332675 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21712955" @default.
• W2077332675 hasPublicationYear "2011" @default.
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