Seth Cheetham

Seth Cheetham

@sethcheetham.bsky.social

mRNA drug discovery | Deputy-Director BASE mRNA Facility | Associate Professor at the University of Queensland.

1K followers178 following51 posts

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Seth Cheetham
@sethcheetham.bsky.social

The greatest challenge for #mRNA-LNP therapies is targeting non-liver tissues. To overcome this, we developed customisable bispecific antibodies to tether mRNA-LNPs to cell-surface proteins, achieving efficient and selective mRNA delivery in vivo. Preprint 👇 t.co/0nJj8eVsqC

Seth Cheetham
@sethcheetham.bsky.social

To accelerate #mRNA vaccine and therapy research, we're excited to share our end-to-end protocol for mRNA design, synthesis and encapsulation in @natprot.nature.com. Protocol development led by @laura-leighton.bsky.social, Natasha Chaudhary and Tim Mercer.@basemrna.bsky.social rdcu.be/eqiF1

rdcu.beThe design, manufacture and LNP formulation of mRNA for research useNature Protocols - This protocol describes simple, small-scale laboratory production of mRNA for research and preclinical use. This includes sequence design, DNA template production, mRNA synthesis...
Seth Cheetham
@sethcheetham.bsky.social

Systemic mRNA-LNP delivery beyond the liver? Check out our recent paper demonstrating cell-specific mRNA-LNP delivery using PEG- and target cell-specific antibodies. This approach can customised to any target cell-type with off-the-shelf mRNA-LNPs. 1/ sciencedirect.com/science/arti...

sciencedirect.comTargeted mRNA delivery with bispecific antibodies that tether LNPs to cell surface markersEfficient delivery of mRNA-lipid nanoparticles (LNPs) to specific cell types remains a major challenge for mRNA therapeutics. Conventional targeting a…
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Seth Cheetham
@sethcheetham.bsky.social

Systemic mRNA-LNP delivery beyond the liver? Check out our recent paper demonstrating cell-specific mRNA-LNP delivery using PEG- and target cell-specific antibodies. This approach can customised to any target cell-type with off-the-shelf mRNA-LNPs. 1/ sciencedirect.com/science/arti...

sciencedirect.comTargeted mRNA delivery with bispecific antibodies that tether LNPs to cell surface markersEfficient delivery of mRNA-lipid nanoparticles (LNPs) to specific cell types remains a major challenge for mRNA therapeutics. Conventional targeting a…
View full thread
Seth Cheetham
@sethcheetham.bsky.social

Systemic mRNA-LNP delivery beyond the liver? Check out our recent paper demonstrating cell-specific mRNA-LNP delivery using PEG- and target cell-specific antibodies. This approach can customised to any target cell-type with off-the-shelf mRNA-LNPs. 1/ sciencedirect.com/science/arti...

sciencedirect.comTargeted mRNA delivery with bispecific antibodies that tether LNPs to cell surface markersEfficient delivery of mRNA-lipid nanoparticles (LNPs) to specific cell types remains a major challenge for mRNA therapeutics. Conventional targeting a…
Seth Cheetham
@sethcheetham.bsky.social

Getting a high dose of mRNA to target tissues is one of the toughest problems for broad use of mRNA-LNP therapies. When administered systemically mRNA-LNPs go the liver with little delivery to other tissues. 2/

Seth Cheetham reposted

Christine Mordstein
@cmordstein.bsky.social

Calling on #ONT #Nanopore #sequencing experts: when sequencing through a stretch of 120nt dA using a DNA plasmid kit (outsourced in our case), what should one expect as average length in the output? The loss we are seeing is a bit extreme #RNAsky

Seth Cheetham
@sethcheetham.bsky.social

#mRNA meets Tardigrades! Delivery of an mRNA encoding a protein from the famously tough animal can protect healthy tissue from damaging radiation. Very creative! #RNAsky www.nature.com/articles/s41...

nature.comRadioprotection of healthy tissue via nanoparticle-delivered mRNA encoding for a damage-suppressor protein found in tardigrades - Nature Biomedical EngineeringRadiation-therapy-induced DNA damage in oral and rectal epithelial cells can be reduced via the nanoparticle-mediated local delivery of messenger RNA encoding for a damage-suppressor protein found in ...
Seth Cheetham
@sethcheetham.bsky.social

New #mRNA cap structures get you more bang (protein) for your buck! Nice new research from @jmcoller.bsky.social in collaboration with Trilink shows the CleanCap M6 analogue inhibits decapping and substantially increases protein expression in vivo. www.cell.com/molecular-th...

cell.comCleanCap M6 inhibits decapping of exogenously delivered IVT mRNAIn this manuscript, Mandell and colleagues present CleanCap M6, a next generation 5’ cap analog that outperforms existing industry standards in live mice. Mandell and colleagues found that this cap ex...
Seth Cheetham
@sethcheetham.bsky.social

Exciting news! @basemrna.bsky.social and Vaxxas have been awarded the $2M USD Biomedical Advanced Research and Development Authority (BARDA) Patch Forward Concept Stage Prize to develop thermostable needle-free mRNA vaccines. www.uq.edu.au/news/article...

uq.edu.auUQ and Vaxxas win prize to advance patch-based mRNA COVID-19 vaccineUQ’s BASE facility and biotechnology company Vaxxas have been announced as stage winners of a prestigious global prize to accelerate a patch-based mRNA vaccine for COVID-19.
Seth Cheetham
@sethcheetham.bsky.social

#mRNA meets cell therapies! It was great to collaborate with Fernando Guimaraes's team to develop mRNA CARs and delivered them to NK cells. NKs transfected with EphA2 CAR mRNA elicited a strong anti-tumour response in animal sarcoma models. onlinelibrary.wiley.com/doi/10.1002/...

onlinelibrary.wiley.comEnhancement of anti‐sarcoma immunity by NK cells engineered with mRNA for expression of a EphA2‐targeted CARHuman NK cells can be efficiently transfected with mRNA to safely express an EphA2-CAR without genomic alterations. EphA2-targeted CAR-NK cells exhibit enhanced cytotoxicity against paediatric sarco...
Seth Cheetham
@sethcheetham.bsky.social

Awesome work from Michael Mitchell's lab at UPenn in @natureportfolio.bsky.social identifies novel LNPs that can deliver #mRNA to the placenta. Using the placenta-targeting LNPs to deliver VEGF mRNA improves pre-eclampsia in animal models. www.nature.com/articles/s41...

nature.comPlacenta-tropic VEGF mRNA lipid nanoparticles ameliorate murine pre-eclampsia - NatureA platform for mRNA lipid nanoparticle delivery to the placenta to treat pre-eclampsia is shown to improve fetal and maternal health in mice and has potential clinical applications in obstetric d...
Seth Cheetham
@sethcheetham.bsky.social

There are more ways to design an mRNA than atoms in the universe, so how do you choose the best one? Our new @basemrna.bsky.social software, mRNArchitect enables you to tune expression, stability, reactogenicity and synthesisability to design more potent #mRNA drugs. www.biorxiv.org/content/10.1...

biorxiv.orgmRNArchitect: optimized design of mRNA sequencesSummary: mRNA design is the critical first step in the development of a new vaccine or therapy. The mRNA primary sequence is assembled from multiple elements, including the coding sequence of the targ...
Seth Cheetham
@sethcheetham.bsky.social

mRNA-encoded transcription factor inhibitors are a rapidly emerging class of drugs. In Science Translational Medicine a team at Harvard treated retinal disease in animals by inhibiting RUNX1. Stay tuned for our forthcoming work targeting cancer transcription factors. www.science.org/doi/10.1126/...

science.orgAn mRNA-encoded dominant-negative inhibitor of transcription factor RUNX1 suppresses vitreoretinal disease in experimental modelsAn mRNA-encoded, dominant-negative inhibitor of RUNX1 exhibits preclinical efficacy in models of ocular diseases.

Seth Cheetham reposted

ARC Tracker
@arc-tracker.bsky.social

ARC says they’ll release the Discovery Projects 2025 outcomes tomorrow. Recently, outcomes announcements have tended to happen at/around 11am Canberra time. My bot will pick up the announcement in RMS’s database and post immediately. Good luck!

Seth Cheetham
@sethcheetham.bsky.social

Cool paper on ribozyme-mediated trans-ligation of mRNAs to deliver larger cargo. I love this concept, but the examples seem a little engineered. We can and do make conventional mRNAs up to 10kb and greater without any problems. Interested in what others think. #RNAsky www.science.org/doi/10.1126/...

science.orgRibozyme-activated mRNA trans-ligation enables large gene delivery to treat muscular dystrophiesRibozymes are small catalytic RNA sequences capable of nucleotide-specific self-cleavage found widespread in nature. Ribozyme cleavage generates distinct 2′,3′-phosphate and 5′-hydroxyl termini that r...
Seth Cheetham
@sethcheetham.bsky.social

Can #mRNA technology rejuvenate aged skin? George Church's lab identified the AP-1 gene ATF3 as a key regulator of skin ageing. Delivering ATF3 mRNA rejuvenated skin cells, boosting collagen production. www.biorxiv.org/content/10.1...

biorxiv.orgHuman skin rejuvenation via mRNAAging is characterized by a gradual decline in function, partly due to accumulated molecular damage. Human skin undergoes both chronological aging and environmental degradation, particularly UV-induce...

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