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A trigger-inducible split-Csy4 architecture for programmable RNA modulation.
Nucleic Acids Res
January 2025
Research Center for Life Sciences Computing, Zhejiang Lab, Kechuang Avenue, Yuhang District, Hangzhou, Zhejiang, 311121, China.
The CRISPR-derived endoribonuclease Csy4 is a popular tool for controlling transgene expression in various therapeutically relevant settings, but adverse effects potentially arising from non-specific RNA cleavage remains largely unexplored. Here, we report a split-Csy4 architecture that was carefully optimized for in vivo usage. First, we separated Csy4 into two independent protein moieties whose full catalytic activity can be restored via various constitutive or conditional protein dimerization systems.
View Article and Find Full Text PDFOAB-14 alleviates mitochondrial impairment through the SIRT3-dependent mechanism in APP/PS1 transgenic mice and N2a/APP cells.
Free Radic Biol Med
January 2025
Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, Liaoning, 110016, PR China. Electronic address:
Alzheimer's disease (AD) is a progressive degenerative disease that affects a growing number of elderly individuals worldwide. OAB-14, a novel chemical compound developed by our research group, has been approved by the China Food and Drug Administration (FDA) for clinical trials in patients with AD (approval no. YD-OAB-220210).
View Article and Find Full Text PDFAffinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.
Proc Natl Acad Sci U S A
January 2025
Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer.
View Article and Find Full Text PDFSmall-molecule inhibition of SARS-CoV-2 NSP14 RNA cap methyltransferase.
Nature
December 2024
Laboratory for RNA Molecular Biology, The Rockefeller University, New York, NY, USA.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid development of highly effective vaccines against SARS-CoV-2 has altered the trajectory of the pandemic, and antiviral therapeutics have further reduced the number of COVID-19 hospitalizations and deaths. Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that encode various structural and non-structural proteins, including those critical for viral RNA replication and evasion from innate immunity.
View Article and Find Full Text PDFd-Amphetamine and Feeding States Cohesively Affect Locomotion and Motor Neuron Response in Zebrafish Larvae.
Brain Behav
December 2024
Department of Mechanical and Industrial Engineering, The University of Illinois at Chicago, Chicago, Illinois, USA.
Purpose: Amphetamine (AMPH) increases locomotor activities in animals, and the locomotor response to AMPH is further modulated by caloric deficits such as food deprivation and restriction. The increment in locomotor activity regulated by AMPH-caloric deficit concomitance can be further modulated by varying feeding schedules (e.g.
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