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Seth Cheetham

@sethcheetham.bsky.social
1.1K followers 178 following 51 posts

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

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Seth Cheetham @sethcheetham.bsky.social · 11/06/2025
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.be
The design, manufacture and LNP formulation of mRNA for research use
Nature 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...
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Seth Cheetham @sethcheetham.bsky.social · 16/05/2025
Today, a huge milestone for personalised #mRNA therapeutics for inherited disease! A baby with an ultra-rare mitochondrial metabolic disease was treated at UPenn with an mRNA-encoded gene-corrector. The mRNA was made to treat a single individual in just 7 months! www.nejm.org/doi/full/10....
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Seth Cheetham @sethcheetham.bsky.social · 02/04/2025
Crucially, this approach doesn't require a new LNP, it works with FDA-approved formulations. We hope that this approach will enable targeted mRNA therapeutics for diverse diseases. Work led by Bettina Dietmair, James Humphries and Chris Howard. @basemrna.bsky.social
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Seth Cheetham @sethcheetham.bsky.social · 02/04/2025
The technology is programmable and works with other targeting arms including anti-PSMA (highly expressed on prostate cancer cells) bispecifics. 6/
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Seth Cheetham @sethcheetham.bsky.social · 02/04/2025
Bispecifics can be used by combining with the mRNA-LNP (pre-mixing) or the bispecific can be administered first (pre-targeting). 5/
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Seth Cheetham @sethcheetham.bsky.social · 02/04/2025
As proof of concept we used anti-EGFR bispecifics to deliver mRNA to mouse breast cancer xenografts. The mRNA-payload (luciferase) is very efficiently delivered in vivo. 4/
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Seth Cheetham @sethcheetham.bsky.social · 02/04/2025
To overcome this obstacle we developed bispecific antibodies that bind to PEG on the surface of LNPs and to cell-surface markers. 3/
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Seth Cheetham @sethcheetham.bsky.social · 02/04/2025
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/
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Seth Cheetham @sethcheetham.bsky.social · 02/04/2025
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.com
Targeted mRNA delivery with bispecific antibodies that tether LNPs to cell surface markers
Efficient 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 · 20/03/2025
Exited to share our latest preprint! mRNA-LNPs are efficiently delivered to healthy livers, but what about liver tumours? Our postdoc @laura-leighton.bsky.social found liver tumours efficiently take up mRNA, enabling next generation mRNA-LNP cancer therapeutics. www.biorxiv.org/content/10.1...
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Reposted by Seth Cheetham
Richard Behringer @rrbehringer.bsky.social · 12/03/2025
Developmental biology research leads to fundamental discoveries for biomedical research. RNA Vaccines. Lane et al., 1971 PMID: 5169490. Images by Brandy Walker & Amaya Moss @rkmille . @socdevbio.bsky.social 3/12
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Seth Cheetham @sethcheetham.bsky.social · 06/03/2025
Happy to sure our protocol if helpful, just send me a DM
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Seth Cheetham @sethcheetham.bsky.social · 06/03/2025
We use q5 which has a very low error rate. We've done a lot of ONTseq of plasmid and pcr templates and don't see any increase in error rate, but we see way better polyA integrity.
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Seth Cheetham @sethcheetham.bsky.social · 06/03/2025
How much mRNA are you producing? We routinely use PCR to generate templates for up to 1-20mg productions. I know people that have done larger batches too.
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Seth Cheetham @sethcheetham.bsky.social · 06/03/2025
There are some tweaks like segmented polyA tails that somewhat reduce deletions, but they're still very frequent. Worse, they are sometimes subclonal so sanger sequencing doesn't even detect the deletion. The field definitely needs better synthetic biology solutions. doi.org/10.1261/rna....
doi.org
Segmented poly(A) tails significantly reduce recombination of plasmid DNA without affecting mRNA translation efficiency or half-life
A monthly journal publishing high-quality, peer-reviewed research on all topics related to RNA and its metabolism in all organisms
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Reposted by Seth Cheetham
Christine Mordstein @cmordstein.bsky.social · 05/03/2025
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
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Seth Cheetham @sethcheetham.bsky.social · 06/03/2025
Could be real though, polyA deletions in plasmids are really common and one of the reasons we switched to PCR-based templates.
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Seth Cheetham @sethcheetham.bsky.social · 06/03/2025
#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.com
Radioprotection of healthy tissue via nanoparticle-delivered mRNA encoding for a damage-suppressor protein found in tardigrades - Nature Biomedical Engineering
Radiation-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 ...
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Seth Cheetham @sethcheetham.bsky.social · 06/03/2025
@helengunter-mrna.bsky.social is the expert at this.
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Seth Cheetham @sethcheetham.bsky.social · 02/03/2025
Not the best weather forecast for Brisbane 😬
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Seth Cheetham @sethcheetham.bsky.social · 26/02/2025
Preach!
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Seth Cheetham @sethcheetham.bsky.social · 31/01/2025
You might be a bit overqualified Scott ;)
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Seth Cheetham @sethcheetham.bsky.social · 31/01/2025
Interested in undertaking a PhD in the transformative field #mRNA cancer vaccines? I have an earmarked #PhD scholarship available for an outstanding domestic student to join our team at UQ and @basemrna.bsky.social. If this sounds like you, get in touch. study.uq.edu.au/study-option...
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Seth Cheetham @sethcheetham.bsky.social · 29/01/2025
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.com
CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA
In 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...
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Seth Cheetham @sethcheetham.bsky.social · 20/01/2025
Wow this is super cool! Single-cell resolution imaging of #mRNA-LNP biodistribution in cleared mouse bodies. www.nature.com/articles/s41...
nature.com
Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning - Nature Biotechnology
An integrated experimental and deep learning pipeline reveals cell-level targeting of nanocarriers in whole bodies.
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Seth Cheetham @sethcheetham.bsky.social · 14/01/2025
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.au
UQ and Vaxxas win prize to advance patch-based mRNA COVID-19 vaccine
UQ’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.
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Seth Cheetham @sethcheetham.bsky.social · 13/01/2025
#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.com
Enhancement of anti‐sarcoma immunity by NK cells engineered with mRNA for expression of a EphA2‐targeted CAR
Human 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...
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Seth Cheetham @sethcheetham.bsky.social · 09/01/2025
Out of office
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Seth Cheetham @sethcheetham.bsky.social · 13/12/2024
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.com
Placenta-tropic VEGF mRNA lipid nanoparticles ameliorate murine pre-eclampsia - Nature
A 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...
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Seth Cheetham @sethcheetham.bsky.social · 09/12/2024
Earlier this year I had the opportunity to present a TEDx talk on the transformative potential of personalised #mRNA vaccines for cancer. The recording is out now: www.youtube.com/watch?v=BnSO... #RNAsky #RNAtx @basemrna.bsky.social
youtube.com
How personalized mRNA vaccines could revolutionize cancer treatment | Seth Cheetham | TEDxUQ
YouTube video by TEDx Talks
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Seth Cheetham @sethcheetham.bsky.social · 06/12/2024
How I imagine our lab animals talk to each other.
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Seth Cheetham @sethcheetham.bsky.social · 06/12/2024
@faulknerlab.bsky.social
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Seth Cheetham @sethcheetham.bsky.social · 04/12/2024
This work was led by @helengunter-mrna.bsky.social who just joined @bsky.app. Follow her for all the latest on mRNA design and mRNA vaccine sequencing.
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Seth Cheetham @sethcheetham.bsky.social · 04/12/2024
Try out the software here: basefacility.org.au/software/
basefacility.org.au
Software - BASE mRNA facility
mRNA design software - mRNArchitect is a software toolkit to design, build and optimise mRNA vaccines and therapies.
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Seth Cheetham @sethcheetham.bsky.social · 04/12/2024
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.org
mRNArchitect: optimized design of mRNA sequences
Summary: 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...
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Seth Cheetham @sethcheetham.bsky.social · 04/12/2024
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.org
An mRNA-encoded dominant-negative inhibitor of transcription factor RUNX1 suppresses vitreoretinal disease in experimental models
An mRNA-encoded, dominant-negative inhibitor of RUNX1 exhibits preclinical efficacy in models of ocular diseases.
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Seth Cheetham @sethcheetham.bsky.social · 03/12/2024
Sure thing Igor
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Seth Cheetham @sethcheetham.bsky.social · 03/12/2024
Super cool work. I worked a lot with MS2 in my PhD and the background was always a challenge.
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Seth Cheetham @sethcheetham.bsky.social · 26/11/2024
Sounds cool. Done
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Seth Cheetham @sethcheetham.bsky.social · 26/11/2024
Done
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Seth Cheetham @sethcheetham.bsky.social · 26/11/2024
Added
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Seth Cheetham @sethcheetham.bsky.social · 25/11/2024
done
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Seth Cheetham @sethcheetham.bsky.social · 25/11/2024
Done
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Seth Cheetham @sethcheetham.bsky.social · 25/11/2024
Done
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Seth Cheetham @sethcheetham.bsky.social · 25/11/2024
I made a starter pack for interesting people in the mRNA vaccines and therapeutics space. Message me if you want to be added. #RNAsky go.bsky.app/VSHfBce
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Reposted by Seth Cheetham
ARC Tracker @arc-tracker.bsky.social · 25/11/2024
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!
Screenshot of a tweet from the ARC saying they’ll announce DP25 grant outcomes tomorrow (Tuesday 26 Nov).
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Seth Cheetham @sethcheetham.bsky.social · 23/11/2024
Hi, could you please me to your starter pack. I work on mRNA therapies for cancer.
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Seth Cheetham @sethcheetham.bsky.social · 23/11/2024
Hi, could you please me to your starter pack. I work on mRNA therapies for cancer.
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Seth Cheetham @sethcheetham.bsky.social · 22/11/2024
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.org
Ribozyme-activated mRNA trans-ligation enables large gene delivery to treat muscular dystrophies
Ribozymes 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...
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Seth Cheetham @sethcheetham.bsky.social · 21/11/2024
Noncoding RNA pioneer Howard Chang will be the new Chief Scientific Officer of Amgen. Interesting move. www.fiercebiotech.com/biotech/amge...
fiercebiotech.com
Amgen taps Stanford's Howard Chang to take CSO reins from Jay Bradner
In a few weeks, Howard Chang, M.D., Ph.D., will join Amgen, filling both the roles of senior vice president of research and chief scientific officer. | In a few weeks, Howard Chang, M.D., Ph.D., will ...
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