ArticleNature communications2023
Rational design of a JAK1-selective siRNA inhibitor for the modulation of autoimmunity in the skin.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39citing papers in PubMed
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39 citing papers in PubMed, 46 citations in OpenAlex.
- Albumin-binding dendrimer-conjugated siRNA enables safe and effective gene silencing throughout the central nervous system.Nucleic acids research · 2026Article
- Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality in an MECP2 duplication mouse model.Nature communications · 2026Article
- The Mechanistic Review of the Molecular Interface of RNA-Loaded Extracellular Vesicles: Redefining Targeted Therapy for Autoimmune Disorders.International journal of molecular sciences · 2026Review
- Vitiligo as a Failure of Immune Resolution and Tissue Regeneration: From Stress Signals to Targeted Immune Modulation.Clinical reviews in allergy & immunology · 2026Review
- RNAi-mediated p38δ silencing mitigates anthracycline cardiotoxicity in female mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Divalent siRNA for prion disease.Nucleic acids research · 2026Article
- IL-11-IL6ST-STAT3 signaling defines a convergent inflammatory axis in esophageal cancer subtypes.Scientific reports · 2026Article
- Beyond inflammation: siRNA strategies for precision targeting in rheumatological disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- The immunology of vitiligo.Nature reviews. Immunology · 2026Review
- Divalent siRNA for prion disease.bioRxiv : the preprint server for biology · 2026Article
- Intradermal delivery of lipophilic siRNAs enables prolonged skin retention and sustained gene silencing in a porcine model.Nature communications · 2026Article
- Albumin-binding dendrimer-conjugated siRNA enables safe and effective gene silencing throughout the central nervous system.bioRxiv : the preprint server for biology · 2025Article
- Recent advances in gene delivery for melanocyte-associated disorders.Advanced drug delivery reviews · 2025Review
- Potent and durable gene modulation in heart and muscle with chemically defined lipophilic siRNAs.Nucleic acids research · 2025Article
- Albumin-binding dendritic siRNA improves delivery and efficacy to solid tumors in a melanoma model.Molecular therapy. Nucleic acids · 2025Article
- Linking IFN-γ-Mediated Pathogenesis to ROCK-Targeted Therapy in a Scalable iPSCs-Based Vitiligo Model.International journal of molecular sciences · 2025Article
- Advances in locally administered nucleic acid therapeutics.Bioactive materials · 2025Review
- A Therapeutic Small-Interfering RNA Potentiates Janus Kinase 1 Modulation for the Treatment of Dog Inflammatory Diseases.ACS pharmacology & translational science · 2025Article
- Transdermal delivery of ultradeformable cationic liposomes complexed with miR211-5p (UCL-211) stabilizes BRAFV600E+ melanocytic nevi.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
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Authors and funding
36 authors at 3 institutions in 2 countries.
Qi TangDepartment of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0002-8913-0519
Hassan H FakihRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0002-7598-0993
Mohammad Zain Ui AbideenRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Samuel R HildebrandRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Khashayar AfshariDepartment of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Katherine Y GrossRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Jacquelyn SousaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Allison S MaebiusProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Christina BartholdyLEO Pharma A/S, Industriparken 55, 2750, Ballerup, Denmark.
Pia Pernille SøgaardLEO Pharma A/S, Industriparken 55, 2750, Ballerup, Denmark.ORCID 0000-0001-9175-1819
Malene JackerottLEO Pharma A/S, Industriparken 55, 2750, Ballerup, Denmark.ORCID 0000-0003-4815-2153
Vignesh HariharanRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0001-9624-1244
Ashley SummersRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0002-5425-0457
Xueli FanDepartment of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Ken OkamuraDepartment of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0001-7366-3233
Kathryn R MonopoliRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0002-8615-4849
David A CooperRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0003-1356-1707
Dimas EcheverriaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Brianna BramatoRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Nicholas McHughRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0003-2004-0811
Raymond C FurgalRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0002-4757-7339
Karen DresserDepartment of Pathology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0002-8599-4352
Sarah J WinterRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Annabelle BiscansRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0001-9953-9265
Jane ChuprinDepartment of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0001-8420-6644
Nazgol-Sadat HaddadiDepartment of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0001-8854-8182
Shany ShermanDepartment of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Ümmügülsüm Yıldız-AltayDepartment of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0001-8774-9257
Mehdi RashighiDepartment of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Jillian M RichmondDepartment of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Claire Bouix-PeterAldena Therapeutics, London, E1 6RA, UK.
Carine BlanchardAldena Therapeutics, London, E1 6RA, UK.ORCID 0000-0002-3377-290X
Adam ClaussLEO Pharma A/S, Industriparken 55, 2750, Ballerup, Denmark.ORCID 0000-0002-6381-324X
Julia F AltermanRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA. Julia.Alterman@umassmed.edu.ORCID 0000-0002-6195-0857
Anastasia KhvorovaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA. Anastasia.Khvorova@umassmed.edu.ORCID 0000-0001-6928-8071
John E HarrisDepartment of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA. John.Harris@umassmed.edu.ORCID 0000-0002-7815-6430
University of Massachusetts Chan Medical School · USLeo Pharma (Denmark) · DKWorcester Polytechnic Institute · US
Funding
Chemical engineering of therapeutic RNAs for extrahepatic deliveryR35GM131839 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ANASTASIA KHVOROVA · 2019 to 2026
$3.1MTreg Migration and Function During Autoimmunity within Peripheral TissueR01AR069114 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI HARRIS, JOHN E · 2015 to 2020
$2.2MTraining in the Molecular Basis of Autoimmunity and AutoinflammationT32AI132152 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Katherine A. Fitzgerald, Ann Marshak-Rothstein · 2018 to 2026
$1.6MBD FACSAriaTM Fusion Fluoresence-Activated Cell SorterS10OD028576 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SCHRADER, CAROL E · 2020 to 2020
$565kMid-Scale RNA Synthesis, Purification and Quality Control SystemS10OD020012 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA · 2015 to 2015
$563kDeveloping a programmable siRNA-based therapeutic platform for gene silencing in the skinK99AR082987 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI TANG, QI · 2023 to 2024
$226kNIAID NIH HHS T32 AI132152NIAMS NIH HHS K99 AR082987NIAMS NIH HHS R01 AR069114NIGMS NIH HHS R35 GM131839NIH HHS S10 OD020012NIH HHS S10 OD028576
Abstract
Inhibition of Janus kinase (JAK) family enzymes is a popular strategy for treating inflammatory and autoimmune skin diseases. In the clinic, small molecule JAK inhibitors show distinct efficacy and safety profiles, likely reflecting variable selectivity for JAK subtypes. Absolute JAK subtype selectivity has not yet been achieved. Here, we rationally design small interfering RNAs (siRNAs) that offer sequence-specific gene silencing of JAK1, narrowing the spectrum of action on JAK-dependent cytokine signaling to maintain efficacy and improve safety. Our fully chemically modified siRNA supports efficient silencing of JAK1 expression in human skin explant and modulation of JAK1-dependent inflammatory signaling. A single injection into mouse skin enables five weeks of duration of effect. In a mouse model of vitiligo, local administration of the JAK1 siRNA significantly reduces skin infiltration of autoreactive CD8
Indexed as
Janus Kinase InhibitorsVitiligoAnimalsAutoimmunityCD8-Positive T-LymphocytesHumansJanus Kinase 1MiceRNA, Double-StrandedRNA, Small InterferingJAK1 protein, humanJanus Kinase 1Janus Kinase InhibitorsRNA, Double-StrandedRNA, Small Interfering
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.