CRISPR Technologies Speaker Max Wilkinson on LINE Mechanisms

The 2023 International Conference on CRISPR Technologies will be held October 17–19, 2023 at the Revere Hotel Boston Common, Boston, MA. Organized by AIChE’s Society for Biological Engineering (SBE), the conference will focus on the latest advances in the genome editing field, bringing together key stakeholders with aligned interests across the spheres of academia and industry. Reserve your spot today.

We spoke with Max Wilkinson, a Postdoctoral Fellow at the Broad Institute, to discuss what he’ll be sharing at the conference, trends in the CRISPR field, and how CRISPR can advance some of the grand challenges facing engineering and society today.

What specifically will you be talking about at the conference?

I’ll present some recent structural and biochemical work on the mechanism of action of long interspersed nuclear element (LINE) retrotransposons. These are the only demonstrably active family of mobile genetic element in human cells and are responsible for producing about 40% of the human genome. Understanding how LINEs work may allow their reprogramming, which could help address a major gap in current genome editing technologies: site-specific insertion of large DNA sequences, especially in post-mitotic cells.

I will show a cryo-EM structure of the R2 retrotransposon from Bombyx mori, a model system for understanding LINE mechanisms. I’ll show how insights from the structure can lead to a proof-of-principle reprogrammed retrotransposon, where Cas9 can guide R2 to integrate arbitrary sequences at arbitrary loci.

How do CRISPR technologies influence/overlap with other areas of bioengineering?

CRISPR overlaps with any area of biology where enzymes need to be programmed by the presence of a specific genetic sequence – so this is not even limited to bioengineering! Anywhere where genetic screens or detectors or circuits or therapeutics are being designed can benefit from considering CRISPR technologies. It’s mainly limited by the creativity of the scientist.

What are some of the technologies trending in the CRISPR field?

CRISPR is quite good at destruction and not as good at creation. Definitely a trend is towards making tools that can insert longer and longer sequences into a genome. A prominent example is prime editing, which is quite limited in the size of the insertions it can make. CRISPR-directed transposons are a really cool new direction to increase the sizes of possible edits.

Overcoming delivery challenges seems to be another big area. Some engineered protein systems take up many kb of sequence space, and so packaging them into AAV or other gene therapy vectors can be a challenge. This is currently being solved by making genome editors smaller through protein engineering or by biological discovery of novel compact systems, and also by developing new delivery vehicles with larger packaging capacity.

How do you envision CRISPR technologies advancing some of the grand challenges in engineering and society (medicine, health informatics, etc.)?

The ability to make any possible change to a genome at any position in any specific cell type would give a ready cure to any disease where a direct causal link is identified between a genetic variant and a phenotype. This could make many untreatable diseases treatable. What then becomes limiting is biological understanding: many diseases do not have direct causal links to single genetic variants – consider Alzheimer’s as just one example. CRISPR technologists and bioengineers will have to sit and wait for the biologists to actually work out what should be corrected by these new technologies: biological understanding is usually so much more important than technological developments to truly advance healthcare, though I suppose they somewhat go hand in hand.

About SBE

Established in 2004, the Society for Biological Engineering is a technological community for engineers and applied scientists integrating biology with engineering. Members of SBE come from a broad spectrum of industries and disciplines and share in SBE’s mission of realizing the benefits of bioprocessing, biomedical, and biomolecular applications. Learn more about SBE. 

Learn more about the 6th International Conference on CRISPR Technologies.

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