The microbes that make up an organism’s microbiome have a range of effects on its health. Scientists use CRISPR systems to genetically manipulate specific bacterial species, for instance those found in the mouse gut microbiome, to find new ways to promote health and treat disease.
(1) Scientists select a specific microbe, such as a bacterial species, for CRISPR-mediated genetic manipulation.
(2) Researchers deliver CRISPR system components using different methods, including conjugation, transformation by heat shock or electroporation, and transduction by bacteriophages.
(3) Scientists directly provide the sequence encoding all CRISPR components, a Cas protein and a guide RNA, into the target microbe.
(4) Alternatively, scientists co-opt the bacteria’s endogenous CRISPR machinery and supply only the guide RNA.
(5) Scientists edit the microbe’s DNA or cause irreparable breaks that lead to DNA degradation.
(6) In bacteria, scientists modify either the plasmid or chromosomal DNA of the microbe. In complex microbial communities such as the gut microbiome, CRISPR-engineered bacteria have multiple applications.
(7) Engineered probiotic bacteria produce modulatory molecules to fight diseases and restore the intestinal flora.
(8) As an antimicrobial, CRISPR self-targets the DNA of a pathogenic bacterial strain.
(9) By CRISPR editing commensal gut bacteria, scientists modulate the effects of these microbes on the microbiome and influence disease related processes such as inflammation.
- Ramachandran G, Bikard D. Editing the microbiome the CRISPR way. Philos Trans R Soc Lond B Biol Sci. 2019;374(1772):20180103.
- Marsh JW, et al. Toward microbiome engineering: expanding the repertoire of genetically tractable members of the human gut microbiome. Annu Rev Microbiol. 2023;77:427-449.
- Wang L, et al. Positive interventional effect of engineered butyrate-producing bacteria on metabolic disorders and intestinal flora disruption in obese mice. Microbiol Spectr. 2022;10(2):e0114721.
- Liu L, et al. CRISPR-Cas-based engineering of probiotics. Biodes Res. 2023;5:0017.
- Jin WB, et al. Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome. Cell. 2022;185(3):547-562.e22.
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