iiinova — where your digital self keeps evolving

Michael Booth @drmikebooth.bsky.social · 22/04/2026

Great to be at the 2026 Synthetic Cell international conference in London! Such a fantastic community to be in ❤️ Thanks to all the organisers @continiclau.bsky.social @syncelleu.bsky.social

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Michael Booth @drmikebooth.bsky.social · 14/04/2026

At last the media is talking about what is really important: single or double unsaturation? 🧪 #chemsky

Jimmy Kimmel video with title "DOPE vs POPE"

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Michael Booth @drmikebooth.bsky.social · 26/02/2026

It was a wonderful experience to receive my Blavatnik Awards in the UK Finalist medal in the gorgeous Banqueting House this week! Then give a public lecture at the Royal Society of Medicine! A giant thank you to the Blavatnik Family Foundation and the The New York Academy of Sciences

Me at the Blavatnik Awards, with my fellow finalists and giving me lecture

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Michael Booth @drmikebooth.bsky.social · 10/02/2026

Exciting news: I've been selected as a Finalist for the Blavatnik Awards in the UK 🧬 🥳 This is an incredible honour and I'm thankful to all my past and present group members, whom I have had the privilege to work with, and my collaborators and mentors www.eurekalert.org/news-release...

Image of all the finalists for the Blavatnik Awards in the UK, which includes my face!!!

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Michael Booth @drmikebooth.bsky.social · 17/12/2025

Had a fantastic group winter day with lunch and bowling! I'm so lucky to have such a lovely bunch of people to get to spend time with 🤗

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Michael Booth @drmikebooth.bsky.social · 09/12/2025

It was exciting to have Prof Jonathan Hall from ETH Zürich visit @uclchemistry.bsky.social today to give a fantastic talk on RNA structure! Such incredibly detailed mechanistic work explained in such a simple manner 🧬❤️

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Michael Booth @drmikebooth.bsky.social · 21/11/2025

Excited to be at the UK Platform for Nucleic Acid Therapies (UPNAT) symposium today at UCL!

Prof Alice Davidson introducing upnat symposium

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Michael Booth @drmikebooth.bsky.social · 12/11/2025

Always great to be at the annual @biochemsoc.bsky.social Synthetic Biology UK conference - today's one is extra special as it's in London and I'm on the organising committee 🫡🫣 #SBUK26 #SBUK2026

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Michael Booth @drmikebooth.bsky.social · 11/11/2025

We had a fantastic group day today - discussing new research ideas and a stimulating trip to the Tate Modern ❤️🧪🧬 It's always so wonderful to spend time with these amazing people #chemsky

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Michael Booth @drmikebooth.bsky.social · 09/10/2025

This is a new one for me #chemsky 🧪 My name has appeared on a published paper that I've had nothing to do with (even using an incorrect version of my email address)! Has this happened to others? If so, what did you do?

Website image of a paper with my name on - that's not mine!

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Michael Booth @drmikebooth.bsky.social · 06/10/2025

Congratulations to Ellen Parkes for passing her PhD viva last week 🥳 - PhD #8 from the Booth group 🤩🤯 ! Massive thanks to Harrison Steel and @akellett.bsky.social for examining #proudPI

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Michael Booth @drmikebooth.bsky.social · 26/09/2025

hands up if you also forgot to 'thinky think' ✋ #chemsky 🧪

5. Hot things can look cold. Thinky think before grabby grab. A chemist who's been burnt before

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Michael Booth @drmikebooth.bsky.social · 06/09/2025

Fantastic talk about the shape of DNA from Zoë Waller at Shankarfest in Cambridge Chemistry - along with some embarrassing photos... 🫣 @drzoewaller.bsky.social

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Michael Booth @drmikebooth.bsky.social · 03/09/2025

Through nanoparticle engineering, we were able to generate a tight ‘off’ state - then could achieve full activation using clinically relevant FDA/EMA-approved magnetic field frequencies 🧲🏥! We hope this will enable synthetic cells for real-world application in the body 🧬🟢

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Michael Booth @drmikebooth.bsky.social · 02/09/2025

By switching out the DNA template for one that encoded a pore protein, we demonstrated magnetically-activated release of a model drug molecule from the synthetic cells! This shows the potential for targeted drug delivery of synthetic cells, using a magnetic field 💊🧬🧲

Figure 5 from paper showing magnetic release of a small molecule

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Michael Booth @drmikebooth.bsky.social · 02/09/2025

By encapsulating these magSNAs into synthetic cells, we managed to magnetically 🧲 activate internal gene expression within a tissue phantom mimic 👻 that is impenetrable by the current state of the art optical and small molecule stimuli!!!

Figure 4 from the paper, showing magnetically activated expression in synthetic cells

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Michael Booth @drmikebooth.bsky.social · 02/09/2025

To achieve this, we generated magnetically-activated spherical nucleic acids, based on the pioneering work from Chad Mirkin and others 💪🟢🧬 For the amazing ‘off’ state we achieved, Ellen developed a whole new SNA purification method!

Figure 2 from paper, showing SNA synthesis

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Michael Booth @drmikebooth.bsky.social · 05/08/2025

We then applied this nuclear targeting Oblimersen ASO in a clinically-relevant acute myeloid leukemia cell model - and observed the improved activity at mRNA and protein level, along with increased chemosensitization in combination with a chemotherapy!

Fig 5, showing increased activity in an AML cell model

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Michael Booth @drmikebooth.bsky.social · 05/08/2025

We then switched to use Oblimersen, an ASO that has reached Phase III clinical trials. We showed increased activity at the mRNA and protein level, and measured nuclear uptake by cell fractionation and immunocytochemistry!

Fig 4 showing oblimersen ASO having a much higher activity and nuclear uptake

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Michael Booth @drmikebooth.bsky.social · 05/08/2025

We then attached a common gene knockdown ASO sequence (MALAT1 - RNase H active) and again saw dramatically increased activity by transfection and gymnosis Using immunocytochemistry, we saw a large increase in the nuclear accumulation - and again, activity was outcompeted with excess small molecule

Fig 3 from paper, improved activity of MALAT1 ASO

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Michael Booth @drmikebooth.bsky.social · 05/08/2025

Using a standard splice switching oligonucleotide, we showed double the activity using transfection and gymnosis! A blockade assay, using the small molecule separately, demonstrated our ASO conjugate was binding the same protein target in the cell

splice switching oligo, showing increased activity.

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Michael Booth @drmikebooth.bsky.social · 05/08/2025

We have dramatically increased splice switching *and* RNase-H ASO activity by conjugating a nuclear importer! Published in JACS (@jacs.acspublications.org ‬) Led by Disha Kashyap, with Tom Milne+@natahub.org ‬ @uclchemistry.bsky.social 🧬🧪 #chemsky pubs.acs.org/doi/10.1021/...

Nuclear import increases ASO activity by by RNase H and splice switching mechanisms

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Michael Booth @drmikebooth.bsky.social · 01/08/2025

We then added a toehold sequence to the oligoPROTAC. By using a third oligo we could turn 'off' the activity through toehold mediated strand displacement After degrading the target protein, we could even use this inhibitor oligo to restore the levels of the degraded protein!

Fig 4 from paper - using a third oligo to turn off the oligoPROTAC, by using toehold mediated strand displacement

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Michael Booth @drmikebooth.bsky.social · 01/08/2025

Excitingly, we found similar activity of our optimal oligoPROTAC to the corresponding small molecule PROTAC (i.e. same warheads but with an alkyl linker) - similar concentration/time profiles, downstream activity, and cell death!

Fig 3 from paper - showing similar activity of the oligoPROTAC with a conventional small molecule PROTAC

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Michael Booth @drmikebooth.bsky.social · 01/08/2025

We observed distance-dependant protein degradation (like a small mol PROTAC) by attaching PROTAC warheads onto non-complementary base pairs at the same end of a double stranded DNA - thereby forming our 'oligoPROTACs'

Fig 2 from paper - distance depend BRD4 degradation from 'oligoPROTACs'

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Michael Booth @drmikebooth.bsky.social · 14/07/2025

It was a privilege to organise the 2025 RSC Nucleic Acids Forum at Burlington House last week - @rscnucleicacids.bsky.social! The NAF has been my favourite event every year, so it was amazing to run it myself! Full crowd, fantastic talks and posters, and a wonderful community 🧬❤️

Me presenting my title slide for the event, with the wonderful sponsors!

an image of the ~130 attendees of the NAF!

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Michael Booth @drmikebooth.bsky.social · 23/06/2025

Demonstrating the application of our lysosomal trafficking oligonucleotides (LyTONs), we achieved potent mRNA+protein knockdown of an important leukaemia target: Menin As previously, this activity was shown to be entirely coming from the lysosome!

Fig 5 from the paper, knockdown of a leukaemia target, Menin, using our LyTONs. Both mRNA and protein levels were monitored.

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Michael Booth @drmikebooth.bsky.social · 23/06/2025

Crucially, using lysosomal inhibitors, we demonstrated that all the extra activity we observed from LyTONs was coming from the lysosome – and that intact lysosomes were vital for their activity This proved the mechanism of action as lysosomal trafficking of the mRNA!

Figure 4 from paper. Lysosome inhibitor bafilomycin completely removed all excess activity. While chloroquine, which bursts lysosomes, has the opposite effect for LyTONs to conventional ASOs!

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Michael Booth @drmikebooth.bsky.social · 23/06/2025

This lysosomal transporter even increased the activity of corresponding state-of-the-art ‘gapmers’, which are conventionally used for gene knockdown (via transfection + gymnosis) -> This dual RNase H and lysosomal activity may be able to improve current ASO therapeutics!

Shows Figure 3 from the paper, where we can boost the activity of gapmer ASO through combined RNase H activity and lysosomal trafficking

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Michael Booth @drmikebooth.bsky.social · 23/06/2025

By conjugating a lysosomal transporter to RNase H-inactive ASOs, we saw increased gene knockdown across multiple cell lines using transfection AND gymnosis!

Figure 2 of our paper, showing increased activity of LyTONs in multiple cells lines

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Michael Booth @drmikebooth.bsky.social · 11/06/2025

The bottom up nucleic acid synthetic biologists have got the moves at #SCNAC2025 - w/ @kgoepfrich.bsky.social 😏 @jamessaenz.bsky.social

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Michael Booth @drmikebooth.bsky.social · 09/06/2025

The #SCNAC2025 nucleic acid chemistry conference starting off in Czech-style by @hoceklab.bsky.social 🧬🗡

Michal Hocek telling us a (very big) sword will be used if we go over time on our talks...

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Michael Booth @drmikebooth.bsky.social · 08/06/2025

Excited to be in Czechia for the SCNAC nucleic acids meeting! This is going to be such a fantastic week of nucleic acid chemistry ❤️🧬🧬🧬🧬🧬❤️

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Michael Booth @drmikebooth.bsky.social · 04/06/2025

Someone should give Aragorn and Gandalf a heads up about what is happening at Euston Station

"Two Towers Site Entrance" sign at Euston Station

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Michael Booth @drmikebooth.bsky.social · 10/04/2025

I'm really excited that ACS Bio & Med Chem Au has made me one of the 2024 Rising Stars in Biological, Medicinal, and Pharmaceutical Chemistry! So much credit goes to my group past and present ❤️ 🧬 What a fantastic list of people to be included with: pubs.acs.org/doi/10.1021/...

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Michael Booth @drmikebooth.bsky.social · 03/04/2025

Really wonderful to be in Cambridge to see the prize lecture of my PhD supervisor Prof Sir Shankar Balasubramanian for his @novonordisk.bsky.social Foundation award - super well deserved for the development of next generation sequencing 🧬🧪❤️🏆 #chemsky

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Michael Booth @drmikebooth.bsky.social · 01/04/2025

Had a fantastic trip to Marburg to give a seminar on our latest work developing nucleic acid conjugates 😊❤️🧬 Thanks to Katharina Höfer for the invite - plus I was so excited to finally meet the amazing @olallalab.bsky.social 🙌

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Michael Booth @drmikebooth.bsky.social · 09/03/2025

Fantastic to be in Heidelberg for our SigSynCell EU Marie Curie Doctoral Network workshop! What a beautiful city, thanks to @kgoepfrich.bsky.social for organising! Excited for the science to start tomorrow 🧑‍🔬

Me in Heidelberg, with the iconic bridge and Castle in the background

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Michael Booth @drmikebooth.bsky.social · 23/02/2025

Name a more iconic bridge. I'll wait.

Schematic of illumina sequencing, including bridge amplification

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Michael Booth @drmikebooth.bsky.social · 18/02/2025

Massive congratulations to @drzoewaller.bsky.social for winning the 2024 @rsc-cbbg.bsky.social Lectureship - today, giving her fantastic award lecture at the 2025 RSC CBBG Forum, in Bristol 🥳🏆

Zoe Waller receiving her RSC CBBG Lectureship

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Michael Booth @drmikebooth.bsky.social · 02/02/2025

No prizes for guessing where I am 🤗 Excited to be meeting up with the amazing Francesco Ricci and talking about our latest research 🥳👨‍🔬

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Michael Booth @drmikebooth.bsky.social · 01/02/2025

Great 😑 now Sensodyne and my dentist are mocking me with left-handed DNA 🤦🏻‍♂️

Bottle of sensodyne tooth paste from my dentist with left-handed DNA on it

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Michael Booth @drmikebooth.bsky.social · 25/01/2025

My 5 yo's ice cream shop definitely has London prices...

Notepad with kids writing saying:
Chocolate ice cream 5 pounds
Vanilla ice cream 4 pounds
Strawberry ice cream 6 pounds

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Michael Booth @drmikebooth.bsky.social · 17/01/2025

has trouble with celsius as well... what a joke

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Michael Booth @drmikebooth.bsky.social · 06/01/2025

How your email finds me, on the first day back at work

Deflated snowman sprawled across a roof, i.e. a Monday

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Michael Booth @drmikebooth.bsky.social · 30/12/2024

I guess you didn't go to the school of Prince and Jimi

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Michael Booth @drmikebooth.bsky.social · 29/12/2024

I walk into the living room and my dad says "there is someone Chemistry on celebrity University Challenge you probably know" - I say something very sarcastic, but then who do I see but the fantastic @sykhalid.bsky.social on the TV! Well done Syma for putting yourself through that!

Syma Khalid on the University of Warwick Celebrity University Challenge Team (scores cut out to remove embarrassment...)

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