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Cell Systems
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What are the current bottlenecks in developing and applying CRISPR technologies?

      I think of CRISPR as being a subset of “adaptive” bacterial systems that promote host survival. These adaptive systems are macromolecular systems that enhance host survival in a myriad of ways: by destroying foreign DNA, by mediating horizontal gene transfer, or even by altering host metabolism, among many other diverse functions. In this sense, CRISPR represents just the tip of the iceberg; there are likely many unexplored and uncharacterized adaptive systems that would be practically useful for genomic manipulation. Therefore, identification and characterization of functionally useful adaptive systems is a major bottleneck in the development of new technologies. Bacterial genomes are fast-evolving. Furthermore, sampling of bacterial genomes is sparse compared to the vast diversity of bacterial species. All of this makes computational identification of novel adaptive systems challenging. High-throughput screens are useful if a suitable assay can be identified. Alternatively, common mechanistic principles can be obtained using biochemical and structural characterization, which could guide identification of adaptive systems.
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