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Engineered transcription-associated Cas9 targeting in eukaryotic cells.
Nat Commun
November 2024
Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, USA.
DNA targeting Class 2 CRISPR-Cas effector nucleases, including the well-studied Cas9 proteins, evolved protospacer-adjacent motif (PAM) and guide RNA interactions that sequentially license their binding and cleavage activities at protospacer target sites. Both interactions are nucleic acid sequence specific but function constitutively; thus, they provide intrinsic spatial control over DNA targeting activities but naturally lack temporal control. Here we show that engineered Cas9 fusion proteins which bind to nascent RNAs near a protospacer can facilitate spatiotemporal coupling between transcription and DNA targeting at that protospacer: Transcription-associated Cas9 Targeting (TraCT).
View Article and Find Full Text PDFIdentification of micro- and nanoplastic particles in postnatal sprague-dawley rat offspring after maternal inhalation exposure throughout gestation.
Sci Total Environ
November 2024
Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA; Environmental and Occupational Health Sciences Institute (EOHSI), Piscataway, NJ 08854, USA. Electronic address:
Micro-nanoplastic particulates (MNPs) have been identified in both indoor and outdoor environments. From these real-world exposures, MNPs have been identified in human fluids and organ tissues, including the placenta and breastmilk. Laboratory studies have identified MNPs are capable of crossing the placental barrier and depositing in fetal tissues; however, it remained unclear if MNPs persist in offspring tissues after birth.
View Article and Find Full Text PDFEngineered transcription-associated Cas9 targeting in eukaryotic cells.
bioRxiv
August 2024
Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY 10016, USA.
DNA targeting Class 2 CRISPR-Cas effector nucleases, including the well-studied Cas9 proteins, evolved protospacer-adjacent motif (PAM) and guide RNA interactions that sequentially license their binding and cleavage activities at protospacer target sites. Both interactions are nucleic acid sequence specific but function constitutively; thus, they provide intrinsic spatial control over DNA targeting activities but naturally lack temporal control. Here we show that engineered Cas9 fusion proteins which bind to nascent RNAs near a protospacer can facilitate spatiotemporal coupling between transcription and DNA targeting at that protospacer: Transcription-associated Cas9 Targeting (TraCT).
View Article and Find Full Text PDFSingle inhalation exposure to polyamide micro and nanoplastic particles impairs vascular dilation without generating pulmonary inflammation in virgin female Sprague Dawley rats.
Part Fibre Toxicol
April 2023
Department of Pharmacology and Toxicology Ernest Mario School of Pharmacy, Environmental and Occupational Health Sciences Institute, Rutgers University, 170 Frelinghuysen Road, 08854, Piscataway, NJ, USA.
Background: Exposure to micro- and nanoplastic particles (MNPs) in humans is being identified in both the indoor and outdoor environment. Detection of these materials in the air has made inhalation exposure to MNPs a major cause for concern. One type of plastic polymer found in indoor and outdoor settings is polyamide, often referred to as nylon.
View Article and Find Full Text PDFA universal deep-learning model for zinc finger design enables transcription factor reprogramming.
Nat Biotechnol
August 2023
Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY, USA.
CysHis zinc finger (ZF) domains engineered to bind specific target sequences in the genome provide an effective strategy for programmable regulation of gene expression, with many potential therapeutic applications. However, the structurally intricate engagement of ZF domains with DNA has made their design challenging. Here we describe the screening of 49 billion protein-DNA interactions and the development of a deep-learning model, ZFDesign, that solves ZF design for any genomic target.
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