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New CRISPR methods with potential for microbiome genome editing

13 December 2021
Appeared in BioNews 1125

Researchers have developed several new approaches using CRISPR to modify the genomes of bacterial populations on a large scale. 

Two landmark studies have reported successfully using CRISPR to alter bacterial genomes within their natural populations. The advances could pave the way for so-called 'community editing', where diverse populations of bacteria are modified simultaneously, and in-situ. 

Currently, CRISPR can only perform targeted edits in one cell-type at a time. Community editing, however, would allow the study of bacterial populations on an unprecedented scale, in a less artificial model. 'Breaking and changing DNA within isolated microorganisms has been essential to understanding what that DNA does,' explained Dr Benjamin Rubin at the University of California (UC) Berkeley, lead author of one study. 

'This work helps bring that fundamental approach to microbial communities, which are much more representative of how these microbes live and function in nature,' he added.

The study from UC Berkeley, published in Nature Microbiology, described two methods of genome editing that could work together to target particular bacterial species within a mixed population. First, the researchers developed a screening technique called ET-Seq (Environmental Transformation Sequencing) to identify bacteria which were most susceptible to genome editing within a population. They then used a modified CRISPR system called DART (DNA-editing all-in-one RNA-guided CRISPR-Cas Transposase) to target specific loci within these bacteria, and insert a barcoded DNA sequence that allowed the researchers to track the bacteria's activity. 

The researchers cultured a community of microbes both from human infant stool and soil, and were able to enrich for strains of E.coli carrying a gene of interest – in this case,  antibiotic resistance genes inserted by DART. Led by Professor Jennifer Doudna, who was awarded the 2020 Nobel Prize in Chemistry for the invention of CRISPR/Cas9 genome editing (see BioNews 1070), the team are hopeful ET-Seq and DART could be used to accelerate research of bacterial communities. 

Elsewhere, at the University of California San Francisco (UCSF), researchers successfully manipulated the composition of the gut microbiome in mice – the first study to alter microbial genomes in living mammals. 

Published in Cell Reports, the researchers used a bacteria-infecting virus called M13 to deliver a destructive CRISPR/Cas9 system to a strain of E.coli they wanted to eliminate from the gut. Following analysis of the mice's faeces, they found that the E.coli strain, which was prominent before M13 targeting, diminished to only one percent of the bacterial population. 

Professor Peter Turnbaugh, senior author of the study at UCSF, described the work as 'the starting point for trying to engineer bacteria within the gut.'

The new techniques developed by UC Berkeley and UCSF have significant implications for microbial research, which relies on being able to isolate and grow bacteria and is not possible for many species. Similarly, it is difficult to study processes where multiple species cooperate, such as in nutrient breakdown. 

The methods could also aid medical research into conditions such as autoimmune disorders, cardiovascular disease and even depression, which are linked to imbalances in the gut microbiome.

'Eventually, we may be able to eliminate genes that cause sickness in your gut bacteria or make plants more efficient by engineering their microbial partners,' summarised Dr Brady Cress, co-author of the UC Berkeley study. 

He added: 'But likely, before we do that, this approach will give us a better understanding of how microbes function within a community.'

CRISPRing the microbiome is just around the corner
Berkeley News |  6 December 2021
CRISPR pioneers Doudna and Banfield introduce microbiome community editing
Genetic Engineering and Biotechnology News |  8 December 2021
DART takes aim at community editing
Nature Microbiology |  6 December 2021
Genetic editing in the microbiome could address a myriad of diseases
Optimist Daily |  1 December 2021
Genome editing for microbiomes available soon through new CRISPR development
The Science Times |  6 December 2021
Gut microbiome genetically edited in live mice for the first time
New Atlas |  28 November 2021
Infecting gut microbes with CRISPR-loaded virus demonstrates potential for microbiome gene editing
University of California San Francisco |  22 November 2021
Phage-delivered CRISPR/Cas9 for strain-specific depletion and genomic deletions in the gut microbiome
Cell Reports |  2 November 2021
Species- and site-specific genome editing in complex bacterial communities
Nature Microbiology |  6 December 2021
14 June 2021 - by Eleanor Taylor 
The genome editing capabilities of the CRISPR/Cas9 approach have created an enormous amount of excitement and an equal amount of concern within the scientific community. It is therefore unsurprising that this contentious form of biotechnology has entered the cultural zeitgeist and become a key topic of public interest...
4 May 2021 - by Devika Sooklall 
This genetic society podcast gives us a brief look into the history of genome editing and the various techniques that have been developed that have led us to where we are today...
2 March 2020 - by Dr Jay Stone 
A common strain of gut bacteria may drive genetic changes that cause bowel cancer, according to research published in Nature...
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