Biology subjects

Thordarson, P.

Publications and source records attributed to Thordarson, P..

4 recordsLinked to original sources

bioRxiv2026

Intranasal oxytocin mRNA-LNP can promote social behaviour and reduce pain

The COVID-19 epidemic and success of mRNA-LNP vaccines demonstrated the transformative potential of mRNA therapeutics. Beyond vaccination, mRNA delivery offers a platform for transient on-demand expression of therapeutic proteins for both rare and common diseases. While delivery of therapeutics to the liver is relatively straightforward, targeted delivery of mRNA-LNPs to the central nervous system (CNS) remains a significant challenge. Here we show that intranasal mRNA-LNP delivery results in localized mRNA cargo uptake and functional expression in the respiratory and olfactory epithelium, where the encoded cargo protein is secreted and can enter the CNS. Guided by genomic data of pain-associated gene expression, we identified secreted proteins as candidate mRNA-encoded analgesics. Intranasal mRNA-LNP encoding a synthetic oxytocin transcript (OXT) resulted in bioactive oxytocin peptide delivery to the CNS. Functionally, intranasal OXT mRNA-LNP enhanced social behaviour and attenuated pain responses across multiple behavioural paradigms, without impairing motor coordination. Importantly, repeated dosing was well tolerated and intranasal mRNA-LNP did not elicit an inflammatory response or alter overall health. Together, these findings establish intranasal mRNA-LNP delivery of secreted ligands as a safe, non-invasive route to target the CNS, unlocking a new class of mRNA therapeutics for pain or other disorders of the brain. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/711938v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@131252aorg.highwire.dtl.DTLVardef@17efb79org.highwire.dtl.DTLVardef@1afe479org.highwire.dtl.DTLVardef@c0f2f5_HPS_FORMAT_FIGEXP M_FIG C_FIG One sentence summaryIntranasal administration of mRNA-LNP enables local transfection in nasal epithelium and subsequent secretion of therapeutic oxytocin peptides into the brain, promoting social interactions and reducing pain.

neuroscience↗

bioRxiv2025

Specificity of the stabilising interaction between intrinsically disordered protein sequences and G-quadruplexes in RNA

Intrinsically disordered regions (IDRs) are present in and essential for the function of nearly all the proteins involved in the regulation, cell and developmental processes. The RGG domain in IDRs binds promiscuously to RNA G-quadruplexes (rG4s), a non-canonical 4-stranded secondary structure that occurs in many transcripts involved in gene regulation. Here we show, using weak binding interactions between a minimal RGG-rich peptide and rG4s, that the IDR selectively templates and stabilises the structure of the human telomeric TERRA rG4, providing a unique pathway to RNA folding that does not rely on high-affinity binding or monovalent cations. Multidimensional NMR and circular dichroism analyses reveal individual nucleotide and amino acid identities determine the specificity of the interaction between RGG peptides and rG4s, explaining how IDRs can selectively recognise RNA over DNA G4s, the high specificity of such interactions in vivo, and the high frequency of monogenic mutations observed in IDRs. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=64 SRC="FIGDIR/small/683336v2_ufig1.gif" ALT="Figure 1"> View larger version (13K): org.highwire.dtl.DTLVardef@71fdeborg.highwire.dtl.DTLVardef@1d55ff1org.highwire.dtl.DTLVardef@18dd57dorg.highwire.dtl.DTLVardef@bb2d6c_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2023

Molecular dissection of the soluble photosynthetic antenna from a cryptophyte alga

Cryptophyte algae have a unique phycobiliprotein light-harvesting antenna that fills a spectral gap in chlorophyll absorption, however, it is unclear how it transfers energy efficiently to photosystems. We show that the cryptophyte Hemiselmis andersenii expresses an energetically complex antenna comprising three distinct spectrotypes of phycobiliprotein with different quaternary structures arising from a diverse subunit family. The bulk of the antenna consists of open quaternary form phycobiliproteins acting as primary photon acceptors, supplemented by novel open-braced forms. The final components are closed forms with a long wavelength spectral feature due to substitution of a single chromophore. We propose that the macromolecular organization of the cryptophyte antennas consists of bulk open and open-braced forms that transfer excitations to photosystems via this bridging closed form phycobiliprotein. One-Sentence SummaryAlgae generate a rainbow of antenna proteins by combining a conserved subunit with different members of a multigene family.

molecular biology↗

bioRxiv2020

Skin protective effects of RM191A, a novel superoxide dismutase mimetic

Superoxide dismutase (SOD) is known to be protective against oxidative stress-mediated skin dysfunction. Here we explore the potential therapeutic activities of RM191A, a novel SOD mimetic, on skin. RM191A is a water soluble, dimeric copper (Cu2+-Cu3+)-centred polyglycine coordination complex. It displays 10-fold higher superoxide quenching activity compared to SOD as well as significant anti-inflammatory activity through beneficial modulation of several significant inflammatory pathways in cells. We tested the therapeutic potential of RM191A in a topical gel using a human skin explant model and observed that it significantly inhibits UV-induced DNA damage in the epidermis and dermis, including cyclobutane pyrimidine dimers (CPD), 8-oxo-guanine (8-oxoG) and 8-nitroguanine (8NGO). RM191A topical gel is found to be safe and non-toxic in mice following month-long daily dosing at 0.19 mL/kg body weight. Moreover, it significantly accelerates excisional wound healing, and reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice. HighlightsO_LISuperoxide dismutase mimetic RM191A is a highly stable copper (Cu2+-Cu3+)-polyglycine coordination complex C_LIO_LIRM191A exhibits potent antioxidant (10-fold more than that of superoxide dismutase) properties in vitro C_LIO_LIRM191A exhibits potent anti-inflammatory properties in vitro and in vivo C_LIO_LIRM191A protects human skin explants against UV-induced oxidative stress and DNA damage C_LIO_LIRM191A is non-toxic and readily bioavailable in mice C_LIO_LIRM191A attenuates TPA-induced skin inflammation and improves wound healing in mice C_LI

physiology↗