Matches in SemOpenAlex for { <https://semopenalex.org/work/W4379212356> ?p ?o ?g. }
- W4379212356 abstract "Abstract Transcriptional and epigenetic regulators shape the chromatin microenvironment and corresponding gene expression during cellular differentiation and homeostasis. Programmable modulators of transcription provide a powerful toolkit for controlling gene dosage in therapeutic applications, but a limited catalog of functional domains constrains their robustness and durability profiles, and large cargo sizes impede clinical delivery. To address these limitations, here we perform high-throughput screening to discover novel classes of transcriptional modulators among human, viral, and archaeal proteomes and characterize their functions in a multitude of endogenous human contexts. We identify compact, potent activators from viral proteomes with exceptional robustness across silent and expressed genes in varied cell types using distinct dCas systems. Insights from predicted 3-dimensional structures and machine learning models enabled us to rationally engineer improved activators, both in potency and persistence. Notably, engineered activators achieved mitotically durable gene activation following transient delivery. Our discovery pipeline provides a predictive rubric for the systematic development of hypercompact activators from unannotated proteomes, yielding superior efficiency and kinetics profiles that broadly expand the epigenetic editing toolkit for therapeutic applications." @default.
- W4379212356 created "2023-06-04" @default.
- W4379212356 creator A5003201400 @default.
- W4379212356 creator A5008946739 @default.
- W4379212356 creator A5027869769 @default.
- W4379212356 creator A5032240160 @default.
- W4379212356 creator A5037788360 @default.
- W4379212356 creator A5051463954 @default.
- W4379212356 creator A5055293662 @default.
- W4379212356 creator A5078851874 @default.
- W4379212356 creator A5092079641 @default.
- W4379212356 date "2023-06-03" @default.
- W4379212356 modified "2023-09-26" @default.
- W4379212356 title "Discovery and engineering of hypercompact epigenetic modulators for durable gene activation" @default.
- W4379212356 cites W1978125302 @default.
- W4379212356 cites W1979647722 @default.
- W4379212356 cites W1987557775 @default.
- W4379212356 cites W1995320511 @default.
- W4379212356 cites W2024584416 @default.
- W4379212356 cites W2031901496 @default.
- W4379212356 cites W2041535798 @default.
- W4379212356 cites W2055461114 @default.
- W4379212356 cites W2060608189 @default.
- W4379212356 cites W2066783444 @default.
- W4379212356 cites W2068363360 @default.
- W4379212356 cites W2072024663 @default.
- W4379212356 cites W2092258256 @default.
- W4379212356 cites W2121417064 @default.
- W4379212356 cites W2123212032 @default.
- W4379212356 cites W2126942185 @default.
- W4379212356 cites W2144091055 @default.
- W4379212356 cites W2160051211 @default.
- W4379212356 cites W2160893019 @default.
- W4379212356 cites W2163173465 @default.
- W4379212356 cites W2223890780 @default.
- W4379212356 cites W2404280981 @default.
- W4379212356 cites W2501443726 @default.
- W4379212356 cites W2562443513 @default.
- W4379212356 cites W2604130415 @default.
- W4379212356 cites W2785429866 @default.
- W4379212356 cites W2785792383 @default.
- W4379212356 cites W2791638592 @default.
- W4379212356 cites W2810261410 @default.
- W4379212356 cites W2881369636 @default.
- W4379212356 cites W2885130586 @default.
- W4379212356 cites W2904738166 @default.
- W4379212356 cites W2912582309 @default.
- W4379212356 cites W2948703559 @default.
- W4379212356 cites W2950199429 @default.
- W4379212356 cites W2980450195 @default.
- W4379212356 cites W2997938055 @default.
- W4379212356 cites W3006116138 @default.
- W4379212356 cites W3007420340 @default.
- W4379212356 cites W3018649179 @default.
- W4379212356 cites W3041760426 @default.
- W4379212356 cites W3141751158 @default.
- W4379212356 cites W3158459025 @default.
- W4379212356 cites W3174474887 @default.
- W4379212356 cites W3194597727 @default.
- W4379212356 cites W3198740632 @default.
- W4379212356 cites W3200045630 @default.
- W4379212356 cites W4210325017 @default.
- W4379212356 cites W4220753724 @default.
- W4379212356 cites W4221027820 @default.
- W4379212356 cites W4221095165 @default.
- W4379212356 cites W4281790889 @default.
- W4379212356 cites W4283699396 @default.
- W4379212356 cites W4285800155 @default.
- W4379212356 cites W4293316025 @default.
- W4379212356 cites W4311917508 @default.
- W4379212356 cites W4317254648 @default.
- W4379212356 cites W4320183133 @default.
- W4379212356 cites W4324045883 @default.
- W4379212356 cites W4327550249 @default.
- W4379212356 cites W4378229099 @default.
- W4379212356 doi "https://doi.org/10.1101/2023.06.02.543492" @default.
- W4379212356 hasPublicationYear "2023" @default.
- W4379212356 type Work @default.
- W4379212356 citedByCount "0" @default.
- W4379212356 crossrefType "posted-content" @default.
- W4379212356 hasAuthorship W4379212356A5003201400 @default.
- W4379212356 hasAuthorship W4379212356A5008946739 @default.
- W4379212356 hasAuthorship W4379212356A5027869769 @default.
- W4379212356 hasAuthorship W4379212356A5032240160 @default.
- W4379212356 hasAuthorship W4379212356A5037788360 @default.
- W4379212356 hasAuthorship W4379212356A5051463954 @default.
- W4379212356 hasAuthorship W4379212356A5055293662 @default.
- W4379212356 hasAuthorship W4379212356A5078851874 @default.
- W4379212356 hasAuthorship W4379212356A5092079641 @default.
- W4379212356 hasBestOaLocation W43792123561 @default.
- W4379212356 hasConcept C104317684 @default.
- W4379212356 hasConcept C104397665 @default.
- W4379212356 hasConcept C152662350 @default.
- W4379212356 hasConcept C165864922 @default.
- W4379212356 hasConcept C191908910 @default.
- W4379212356 hasConcept C41091548 @default.
- W4379212356 hasConcept C54355233 @default.
- W4379212356 hasConcept C60644358 @default.
- W4379212356 hasConcept C63479239 @default.
- W4379212356 hasConcept C70721500 @default.