Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308697579> ?p ?o ?g. }
- W4308697579 abstract "Transgenic animals with increased or abrogated target gene expression are powerful tools for drug discovery research. Here, we developed a CRISPR-based Rosa26-LSL-dCas9-VPR mouse model for targeted induction of endogenous gene expression using different Adeno-associated virus (AAV) capsid variants for tissue-specific gRNAs delivery. To show applicability of the model, we targeted low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9), either individually or together. We induced up to ninefold higher expression of hepatocellular proteins. In consequence of LDLR upregulation, plasma LDL levels almost abolished, whereas upregulation of PCSK9 led to increased plasma LDL and cholesterol levels. Strikingly, simultaneous upregulation of both LDLR and PCSK9 resulted in almost unaltered LDL levels. Additionally, we used our model to achieve expression of all α1-Antitrypsin (AAT) gene paralogues simultaneously. These results show the potential of our model as a versatile tool for optimized targeted gene expression, alone or in combination." @default.
- W4308697579 created "2022-11-14" @default.
- W4308697579 creator A5006481802 @default.
- W4308697579 creator A5010152547 @default.
- W4308697579 creator A5028480288 @default.
- W4308697579 creator A5047191042 @default.
- W4308697579 creator A5048286958 @default.
- W4308697579 creator A5054220498 @default.
- W4308697579 creator A5087280259 @default.
- W4308697579 date "2022-11-10" @default.
- W4308697579 modified "2023-09-26" @default.
- W4308697579 title "Rosa26-LSL-dCas9-VPR: a versatile mouse model for tissue specific and simultaneous activation of multiple genes for drug discovery" @default.
- W4308697579 cites W1529408079 @default.
- W4308697579 cites W1649914760 @default.
- W4308697579 cites W1857205731 @default.
- W4308697579 cites W1907349304 @default.
- W4308697579 cites W1962046992 @default.
- W4308697579 cites W1987486422 @default.
- W4308697579 cites W1991543373 @default.
- W4308697579 cites W1998790756 @default.
- W4308697579 cites W2003634176 @default.
- W4308697579 cites W2008289270 @default.
- W4308697579 cites W2014585251 @default.
- W4308697579 cites W2024110748 @default.
- W4308697579 cites W2024704386 @default.
- W4308697579 cites W2032435016 @default.
- W4308697579 cites W2035099895 @default.
- W4308697579 cites W2036828042 @default.
- W4308697579 cites W2040059531 @default.
- W4308697579 cites W2042257807 @default.
- W4308697579 cites W2048162805 @default.
- W4308697579 cites W2054610237 @default.
- W4308697579 cites W2058561890 @default.
- W4308697579 cites W2058640589 @default.
- W4308697579 cites W2065346498 @default.
- W4308697579 cites W2068427957 @default.
- W4308697579 cites W2073874826 @default.
- W4308697579 cites W2075230442 @default.
- W4308697579 cites W2081052882 @default.
- W4308697579 cites W2081832076 @default.
- W4308697579 cites W2091564445 @default.
- W4308697579 cites W2103081715 @default.
- W4308697579 cites W2109751467 @default.
- W4308697579 cites W2116775546 @default.
- W4308697579 cites W2117011155 @default.
- W4308697579 cites W2121550703 @default.
- W4308697579 cites W2140622082 @default.
- W4308697579 cites W2142972494 @default.
- W4308697579 cites W2159741565 @default.
- W4308697579 cites W2159789034 @default.
- W4308697579 cites W2163173465 @default.
- W4308697579 cites W2165564744 @default.
- W4308697579 cites W2175297783 @default.
- W4308697579 cites W2203807603 @default.
- W4308697579 cites W2286099491 @default.
- W4308697579 cites W2344533005 @default.
- W4308697579 cites W2400411104 @default.
- W4308697579 cites W2404313081 @default.
- W4308697579 cites W2487012890 @default.
- W4308697579 cites W2515115069 @default.
- W4308697579 cites W2523099503 @default.
- W4308697579 cites W2558177706 @default.
- W4308697579 cites W2568134927 @default.
- W4308697579 cites W2727482182 @default.
- W4308697579 cites W2749176947 @default.
- W4308697579 cites W2783322400 @default.
- W4308697579 cites W2792803089 @default.
- W4308697579 cites W2888908334 @default.
- W4308697579 cites W2899810284 @default.
- W4308697579 cites W2904738166 @default.
- W4308697579 cites W2910366994 @default.
- W4308697579 cites W2911855152 @default.
- W4308697579 cites W2913212173 @default.
- W4308697579 cites W2915941065 @default.
- W4308697579 cites W2934227337 @default.
- W4308697579 cites W2941499827 @default.
- W4308697579 cites W2946081735 @default.
- W4308697579 cites W2950733835 @default.
- W4308697579 cites W2966022850 @default.
- W4308697579 cites W2971526317 @default.
- W4308697579 cites W2971545397 @default.
- W4308697579 cites W2989040661 @default.
- W4308697579 cites W3003153304 @default.
- W4308697579 cites W3014163326 @default.
- W4308697579 cites W3028545429 @default.
- W4308697579 cites W3030089399 @default.
- W4308697579 cites W3088294075 @default.
- W4308697579 cites W3092444985 @default.
- W4308697579 cites W3127586962 @default.
- W4308697579 cites W3133908480 @default.
- W4308697579 cites W3139186603 @default.
- W4308697579 cites W3153922391 @default.
- W4308697579 cites W3163083257 @default.
- W4308697579 cites W3164839092 @default.
- W4308697579 cites W3190049048 @default.
- W4308697579 cites W3199720718 @default.
- W4308697579 cites W91327126 @default.
- W4308697579 doi "https://doi.org/10.1038/s41598-022-23127-7" @default.
- W4308697579 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36357523" @default.
- W4308697579 hasPublicationYear "2022" @default.