Thread by @Street_Research

So glad to finally be able to share nanofiber micelleplexes with the world! 😀 pubs.acs.org/doi/10.1021/ja…. It turns out #tinysticks are good at delivering #DNA into cells! I just wanted to celebrate with a short 🧵 on how this work arose. 1/13:

Back in 2017 whilst finishing my PhD on anti-cancer #Gquadruplex ligands with @MCGalan_Bristol, I became very interested in nucleic acid therapeutics and technologies such as #CRISPR. Approaches like cancer immunotherapy seemed to me an elegant way of treating disease. 2/13

However, many of the problems facing these exciting areas of research lay in biology. As a synthetic chemist I was unsure of what I could do to help. 3/13

This changed when I read an article in @cenmag that discussed the challenges of delivering NA therapies into cells: cen.acs.org/articles/95/i7… This also goes to show the important role #scientificjournalism has in inspiring people to help solve problems. 4/13

At the time, I knew that the @mannersresearch group was working on precision polymer nanomaterials at @Bristolchem, using a process called CDSA. I thought it would be VERY interesting to try to develop precision 1D polymer nanofibers for DNA delivery in the Manners lab. 5/13

Luckily for me, we were in a good position to begin this project due to the work John Finnegan had been doing on the CDSA of polycarbonates: pubs.acs.org/doi/10.1021/ja…. 6/13

I had also heard about a very interesting funding opportunity from @EPSRC, the #DoctoralPrize Fellowship. I was lucky enough to be awarded one by @BristolUni to undertake this work. 7/13

If I am honest, I wasn’t sure what the future held for me at this point – I would almost certainly have left academic research if I hadn’t got the @EPSRC fellowship. So, the fellowship did its intended job of retaining doctoral students in research careers! 8/13

A key challenge was producing a polymer system that could undergo CDSA into length-controlled nanofibers whilst also being able to complex DNA🧬. Luckily, PFTMC-b-PDMAEMA did the trick. Studying the complexation of DNA was also tricky – we have a paper on this coming soon! 9/13

I naively thought that transfection would be as simple as mixing polymer & DNA, and adding them to cells… Boy, was I wrong! It turns out it is so much more complicated, and now I can appreciate first-hand why cellular transfection & DNA delivery remain so challenging. 10/13

My first successful transfection experiment was back in 2019, but like much science it immediately stopped working. A move to Canada and funding from @NSERC_CRSNG allowed us to understand the system in more detail. Aggregation was another key challenge we had to overcome. 11/13

It wasn’t until 2021 in collaboration with the @Drwillerth lab that we were finally able to reliably transfect cells with micelleplexes. Luckily for us, the results were very interesting! Short nanofiber micelleplexes appear to be potent DNA delivery vehicles 😄🚚🧬12/13

There is much work still to do, but I think the future looks very promising for these delivery vehicles. If you got this far, thanks a lot for reading this thread! I would happily answer any questions anyone might have 😊👨‍🔬 13/13

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