Gene Editing Meets Nanomedicine: A Trustworthy Friendship? | Vittoria Raffa

What if gene editing went on a date with nanomedicine?

Today I am lucky to spend some time talking to my former mentor Vittoria Raffa about all the fundamental molecular biology of gene editing, and the open challenges to translate CRISPR-based technologies to the clinic. Will nanomedicine and synthetic biology be the right partners for gene editing to make it? Vittoria is an Associate Professor of Nanomedicine and Molecular Biology at the University of Pisa, and she’s been a leader in nanomedicine since a very young age.

Vittoria and I start from her experience as the coordinator of the European project I-GENE, which provides a great example to today’s episode, as it combines gene editing, nanomedicine, and synthetic biology concepts. The I-GENE Project is building, specifically, a light-switchable nanoformulation for gene editing, to be first used for melanoma. Vittoria and I discuss the main CRISPR-based technologies, including “traditional” editing with CRISPR/Cas9 and its natural and evolved or engineered variants, base editors, prime editors, PASTE editors, CRISPRa/i. We consider the main open challenges to broadly translate gene editing to the clinic: delivery, off-target toxicity, immunogenicity, cost, and more. Vittoria beautifully explains why the current number of 26 clinical trials, even if huge for how long ago this technology was invented, is less than what can be done: CRISPR-based gene editors are mostly delivered by viral vectors, which cost a lot to make. She suggests that the widespread deployment of nanomedical devices could greatly reduce the cost of therapies, hence accelerating the development of CRISPR medicines for more and more diseases, and at an affordable cost. She then guides us through recent concepts in synthetic biology, especially to build nanomedical tools that recognize multiple cellular inputs and release the drug, such as the gene editor, only when a number of logic gates turn true. I’ll stop here, there’s so much more to discover in our conversation! Looking forward to seeing what Vittoria and the Raffa lab achieve in the next few years!

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[ACADEMIC, outstanding review on most of the state of the gene editing field with a focus on medical applications] Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors: https://www.nature.com/articles/s41587-020-0561-9

[ACADEMIC REVIEW] CRISPR/Cas9 in the era of nanomedicine and synthetic biology: https://www.sciencedirect.com/science/article/pii/S1359644622003683

The I-GENE Project that Vittoria coordinates: https://i-geneproject.eu/

[OUTREACH] CRISPR clinical trials, 2022 Update by the Innovative Genomics Institute: https://innovativegenomics.org/news/crispr-clinical-trials-2022/