September
15,
2023
(Drug ACTION Specific Seminar)
The advent of CRISPR-based technologies has revolutionized our ability to manipulate the genetic content of organisms across the tree of life, and democratized genome editing across the globe. Repurposed from obscure adaptive immune systems in bacteria, CRISPR molecular machines have been broadly deployed in academia and industry in the past 10 years, to manipulate the genomes of organisms relevant to medicine, biotechnology and agriculture. We now have access to a portable CRISPR toolbox enabling flexible editing from a single nucleotide to large scale genome manipulation in organisms that span minimalistic viruses to large trees and their corresponding genome range and complexities. These CRISPR effectors can be multiplexed (concurrently or iteratively) and intermixed using orthogonal systems that enable combinatorial alterations to generate diverse outcomes and edit types. So far, most applications focus on the design of efficacious and safe gene and cell therapies to address human disease. Yet, there are un(der)-appreciated opportunities to deploy genome editing modalities to manipulate the virome and microbiome, and broaden the implementation spectrum at the scale of forestry, with applicable space and time opportunities and caveats. I will discuss recent advances in engineering of phages and bacteria spanning 1nt base editors from single Cas effectors, to >100,000bp manipulations and island engineering using Cascade-Cas3 and CRISPR-associated Tn7-like transposons, spanning CRISPR-Cas systems classes and types, in endogenous and exogenous contexts. I will also highlight the practical limitations and implications of scaling up genome editing, showcasing the path to sustainable agriculture by 2030, next-generation therapies by 2040 and breeding healthier forests by 2050. Besides the technical bottlenecks inherent to the deployment of CRISPR across phylogenetic units, it is necessary to also account for regulatory frameworks, intellectual property pursuit, public engagement, consumer acceptance and geopolitical issues impacting our practical ability to harness genome editing to address medical, agricultural and environmental challenges that require such disruptive technologies.
Hosted by Jason Peters
