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Research group Group Spetz

We are exploring basic mechanisms regarding a group of small non-coding oligonucleotides and their therapeutic potential. We have discovered that a set of single-stranded oligonucleotides temporarily inhibit certain endocytic pathways and thereby modulate innate immune responses as well as providing anti-viral effects.

Group description

The innate immune system is rapidly responding to defend against incoming pathogens, but also has to be balanced to avoid unwanted autoimmune reactions. We have discovered a pool of small non-coding single-stranded oligonucleotides with capacity to dampen signaling from endosomes containing TLR3,7, or 4. In addition, these oligonucleotides provide antiviral effects by inhibiting binding and/or entry of several viral families. We are now mapping local immune responses in the lungs and in the skin after treatment with a drug candidate non-coding oligonucleotide.

Group members

Group managers

Anna-Lena Spetz

Professor

Department of Molecular Biosciences, The Wenner-Gren Institute

08-16 42 05

anna-lena.spetz@su.se

Members

Kevin Memsuri

Student

Department of Molecular Biosciences, The Wenner-Gren Institute

kevin.memsuri@su.se

James Trumbo

Phd Student

Department of Molecular Biosciences, The Wenner-Gren Institute

james.trumbo@su.se

Kahkashan Kamal

PhD student

Department of Molecular Biosciences, The Wenner-Gren Institute

kahkashan.kamal@su.se

Research projects

Publications

Synergistic antiviral activity against drug-resistant HIV-1 by naturally occurring dipeptide and A

single-stranded oligonucleotide. Ceña-Diez R, Spetz AL, Sönnerborg A. Drug Resist Updat. 2023 Mar 4;68:100955. doi: 10.1016/j.drup.2023.100955. Online ahead of print.PMID: 36878096

Advanced Molecular Tweezers with Lipid Anchors against SARS-CoV-2 and Other Respiratory Viruses

Weil T, Kirupakaran A, Le MH, Rebmann P, Mieres-Perez J, Issmail L, Conzelmann C, Müller JA, Rauch L, Gilg A, Wettstein L, Groß R, Read C, Bergner T, Pålsson SA, Uhlig N, Eberlein V, Wöll H, Klärner FG, Stenger S, Kümmerer BM, Streeck H, Fois G, Frick M, Braubach P, Spetz AL, Grunwald T, Shorter J, Sanchez-Garcia E, Schrader T, Münch J. JACS Au. 2022 Sep 6;2(9):2187-2202. doi: 10.1021/jacsau.2c00220. eCollection 2022 Sep 26.PMID: 36186568

Inhibition of Respiratory Syncytial Virus Infection by Small Non-Coding RNA Fragments.

Pålsson, S.A.; Sekar, V.; Kutter, C.; Friedländer, M.R.; Spetz, A.-L. Int. J. Mol. Sci. 2022, 23, 5990.

Macromolecular Viral Entry Inhibitors as Broad-Spectrum First-Line Antivirals with Activity against

SARS-CoV-2. Groß R, Dias Loiola LM, Issmail L, Uhlig N, Eberlein V, Conzelmann C, Olari LR, Rauch L, Lawrenz J, Weil T, Müller JA, Cardoso MB, Gilg A, Larsson O, Höglund U, Pålsson SA, Tvilum AS, Løvschall KB, Kristensen MM, Spetz AL, Hontonnou F, Galloux M, Grunwald T, Zelikin AN, Münch J. Adv Sci (Weinh). 2022 May 11:e2201378. doi: 10.1002/advs.202201378. Epub ahead of print. PMID: 35543527.

Is There a Role for Immunoregulatory and Antiviral Oligonucleotides Acting in the Extracellular

Space? A Review and Hypothesis. Dondalska A, Axberg Pålsson S, Spetz AL. Int J Mol Sci. 2022 Nov 23;23(23):14593. doi: 10.3390/ijms232314593.PMID: 36498932

Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection.

6. Pålsson SA, Dondalska A, Bergenstråhle J, Rolfes C, Björk A, Sedano L, Power UF, Rameix-Welti MA, Lundeberg J, Wahren-Herlenius M, Mastrangelo P, Eleouet JF, Le Goffic R, Galloux M, Spetz AL. Front Immunol. 2020 Sep

Amelioration of Compound 48/80-Mediated Itch and LL-37-Induced Inflammation by a Single-Stranded

Oligonucleotide. Dondalska A, Rönnberg E, Ma H, Pålsson SA, Magnusdottir E, Gao T, Adam L, Lerner EA, Nilsson G, Lagerström M, Spetz AL. Front Immunol. 2020 Sep

A Single-Stranded Oligonucleotide Inhibits Toll-Like Receptor 3 Activation and Reduces Influenza A

(H1N1) Infection. Poux C, Dondalska A, Bergenstråhle J, Pålsson S, Contreras V, Arasa C, Järver P, Albert J, Busse DC, LeGrand R, Lundeberg J, Tregoning JS, Spetz AL. Front Immunol. 2019 Sep 12;10:2161.

The Viral Protein Corona Directs Viral Pathogenesis and Amyloid Aggregation.

Ezzat, K, Pernemalm, M, Pålsson, S, Roberts, T.C, Järver,P, Dondalska,A, Bestas,B, Sobkowiak,M.J, Levänen,B, Sköld,M, Thompson,E.A, Saher,O, Kari,O.K, Lajunen,T, Sverremark Ekström,E, Nilsson,C, Ishchenko,Y, Malm,T, Wood,M.J.A, Power,U.F, Masich,S, Lindén,A, Sandberg,J.K, Lehtiö,J, Spetz,A.L*, Samir EL Andaloussi, S.EL.* Nat Commun. 2019 May 27;10(1). Spetz, AL corresponding author. *Equal contribution.

Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with

Clathrin-Mediated Endocytosis. Järver P, Dondalska A, Poux C, Sandberg A, Bergenstråhle J, Sköld AE, Dereuddre-Bosquet N, Martinon F, Pålsson S, Zaghloul E, Brodin D, Sander B, Lennox KA, Behlke MA, El-Andaloussi S, Lehtiö J, Lundeberg J, LeGrand R, Spetz AL. Sci Rep. 2018 Oct 26;8(1):15841.

Early Resistance of Non-virulent Mycobacterial Infection in C57BL/6 Mice Is Associated With Rapid

Up-Regulation of Antimicrobial Cathelicidin Camp. Adam L, López-González M, Björk A, Pålsson S, Poux C, Wahren-Herlenius M, Fernández C, Spetz AL. Front Immunol. 2018 Sep 3;9:1939. doi: 10.3389/fimmu.2018.01939. eCollection 2018.PMID: 30233570

Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein

Uchtenhagen H, Schiffner T, Bowles E, Heyndrickx L, LaBranche C, Applequist SE, Jansson M, De Silva T, Back JW, Achour A, Scarlatti G, Fomsgaard A, Montefiori D, Stewart-Jones G, Spetz AL. J Immunol. 2014 Jun 15;192(12):5802-12

IFN-α induces APOBEC3G, F, and A in immature dendritic cells and limits HIV-1 spread to CD4+ T cells

Mohanram,V., Sköld,A.E., Bächle, S.M., Pathak,S.K., Spetz, AL. J Immunol. 2013 Apr 1;190(7):3346-53

Single-stranded DNA oligonucleotides inhibit TLR3-mediated responses in human monocyte-derived

dendritic cells and in vivo in cynomolgus macaques. Sköld AE, Hasan M, Vargas L, Saidi H, Bosquet N, Le Grand R, Smith CI, Spetz AL. Blood. 2012 Jul 26;120(4):768-77. Epub 2012 Jun 13.

Immunization with Apoptotic Pseudovirus Transduced Cells Induces both Cellular and Humoral

Responses: a Proof-of-Concept study in Macaques. 15. Koopman,G., Beenhakker,N., Hofman,S., Walther-Jallow,L., Mäkitalo,B., Mooij,P., Anderson,J., Verschoor,E., Bogers,W., Heeney,J.L., Spetz, AL. Vaccine, 2012 Mar 28;30(15):2523-34

Generation of Neutralizing Antibodies and Divergence of SIVmac239 in Cynomolgus Macaques Following

Short-term Early Antiretroviral Therapy. Özkaya Şahin,G, Bowles,E.J.,Parker,P, Uchtenhagen,H, Sheik-Khalil, E., Taylor, S., Pybus,O., Mäkitalo, B.,Walther Jallow,L., Spångberg,M., Thorstensson,R., Achour,A., Fenyö,E.-M., Stewart-Jones,G., and Spetz AL. PLoS Pathogens 2010 Sep 2;6(9):e1001084

HIV-1 infected dendritic cells up-regulate cell surface markers but fail to produce IL-12p70 in

response to CD40 ligand stimulation. Smed Sörensen, A., Lore, K., Walther-Jallow, L., Andersson, J., and Spetz, AL. 2004 Blood 104;1-8

Horizontal transfer of oncogenes by uptake of apoptotic bodies

Bergsmedh,A., Szeles, A., Henriksson, M., Bratt, A., Folkman, J., Spetz, AL. and Holmgren, L. 2001 Proc. Natl. Acad. Sci. 98;6407-6411

T cell subsets in normal human epidermis

Spetz, AL., Strominger, J.L. and Groh-Spies, V. 1996 Am.J.Pathol. 149; 665-674

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