Multispecies-targeting siRNAs for the modulation of JAK1 in the skin.

Autor:	Tang Q; RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.; Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA., Gross KY; RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA., Fakih HH; RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA., Jackson SO; RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA., Zain U I Abideen M; RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA., Monopoli KR; RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.; Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA 01609, USA., Blanchard C; Aldena Therapeutics, London E1 6RA, United Kingdom., Bouix-Peter C; Aldena Therapeutics, London E1 6RA, United Kingdom., Portal T; Aldena Therapeutics, London E1 6RA, United Kingdom., Harris JE; Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA., Khvorova A; RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA., Alterman JF; RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Nucleic acids [Mol Ther Nucleic Acids] 2024 Jan 09; Vol. 35 (1), pp. 102117. Date of Electronic Publication: 2024 Jan 09 (Print Publication: 2024).
DOI:	10.1016/j.omtn.2024.102117
Abstrakt:	Identifying therapeutic oligonucleotides that are cross-reactive to experimental animal species can dramatically accelerate the process of preclinical development and clinical translation. Here, we identify fully chemically-modified small interfering RNAs (siRNAs) that are cross-reactive to Janus kinase 1 (JAK1) in humans and a large variety of other species. We validated the identified siRNAs in silencing JAK1 in cell lines and skin tissues of multiple species. JAK1 is one of the four members of the JAK family of tyrosine kinases that mediate the signaling transduction of many inflammatory cytokine pathways. Dysregulation of these pathways is often involved in the pathogenesis of various immune disorders, and modulation of JAK family enzymes is an effective strategy in the clinic. Thus, this work may open up unprecedented opportunities for evaluating the modulation of JAK1 in many animal models of human inflammatory skin diseases. Further chemical engineering of the optimized JAK1 siRNAs may expand the utility of these compounds for treating immune disorders in additional tissues. Competing Interests: A.K. is a founder of Atalanta Therapeutics and Comanche Biopharma; serves on the Scientific Advisory Board of Aldena Therapeutics, Prime Medicine, Alltrna, and Evox Therapeutics; and owns equities in RXi Pharmaceuticals and Advirna. J.E.H. owns equities in Rheos Medicines, and is a founder of Villaris Therapeutics, Aldena Therapeutics, NIRA Biosciences, Vimela Therapeutics, and Klirna Therapeutics. Q.T., H.H.F., K.Y.G., M.Z.U.I.A., K.R.M., J.E.H., A.K., and J.F.A. are listed as inventors of RNAi technology patents and patent applications. C.B., C.B.-P., and T.P. are executives of Aldena Therapeutics.
Databáze:	MEDLINE
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