Seth Cheetham
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sethcheetham.bsky.social
Seth Cheetham
@sethcheetham.bsky.social
mRNA drug discovery | Deputy-Director BASE mRNA Facility | Associate Professor at the University of Queensland.
Pinned
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
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
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...
rdcu.be
June 10, 2025 at 11:39 PM
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....
May 16, 2025 at 4:36 AM
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...
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…
sciencedirect.com
April 2, 2025 at 4:26 AM
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...
March 20, 2025 at 4:38 AM
Reposted by Seth Cheetham
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
March 12, 2025 at 9:02 PM
Reposted by Seth Cheetham
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
March 5, 2025 at 2:54 PM
#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...
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 ...
www.nature.com
March 6, 2025 at 7:39 AM
Not the best weather forecast for Brisbane 😬
March 2, 2025 at 7:34 AM
Preach!
February 26, 2025 at 9:07 PM
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...
January 31, 2025 at 5:41 AM
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...
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...
www.cell.com
January 29, 2025 at 12:57 AM
Wow this is super cool! Single-cell resolution imaging of #mRNA-LNP biodistribution in cleared mouse bodies.

www.nature.com/articles/s41...
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.
www.nature.com
January 20, 2025 at 8:15 PM
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 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.
www.uq.edu.au
January 14, 2025 at 5:35 AM
#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/...
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...
onlinelibrary.wiley.com
January 13, 2025 at 3:22 PM
Out of office
January 9, 2025 at 3:04 PM
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...
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...
www.nature.com
December 13, 2024 at 6:17 AM
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
How personalized mRNA vaccines could revolutionize cancer treatment | Seth Cheetham | TEDxUQ
YouTube video by TEDx Talks
www.youtube.com
December 9, 2024 at 10:55 PM
How I imagine our lab animals talk to each other.
December 6, 2024 at 6:13 AM
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...
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...
www.biorxiv.org
December 4, 2024 at 10:19 PM
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/...
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.
www.science.org
December 4, 2024 at 4:11 AM
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
November 25, 2024 at 5:57 AM
Reposted by Seth Cheetham
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!
November 25, 2024 at 12:04 AM
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/...
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...
www.science.org
November 22, 2024 at 4:27 AM
Noncoding RNA pioneer Howard Chang will be the new Chief Scientific Officer of Amgen. Interesting move.

www.fiercebiotech.com/biotech/amge...
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 ...
www.fiercebiotech.com
November 21, 2024 at 2:49 AM
We're building Australia's first centre for the designing and manufacturing personalised cancer vaccines at the BASE mRNA facility. On the PhaseIII podcast I discuss the transformative potential of mRNA for cancer and our efforts to bring this tech to patients.

podcasts.apple.com/au/podcast/v...
VAXXED: Game on, with BASE and WEHI
Podcast Episode · Phase III · 19/11/2024 · 26m
podcasts.apple.com
November 19, 2024 at 11:25 PM