Advancing CRISPR applications: here, there and everywhere

BioTechniques News
Jade Parker

CRISPR (clustered regularly interspaced short palindromic repeats) is a technology that allows for the selective modification of living organisms’ DNA.

This technique has a brief history compared to other life science techniques, yet it has quickly made its mark on the research world, receiving recognition during the 2020 Nobel Prizes. Recently, CRISPR has transformed the therapeutic drug discovery field, illuminating drug targets for diseases such as cancer and sickle cell anemia. Beyond its application in therapeutic drug discovery, it has been involved in promoting gut health, mapping the human immune response and enhancing optothermal nanotweezers.

Molecular mapping the immune response

Researchers at Gladstone Institutes (CA, USA) have mapped the human immune response using next-generation CRISPR technology known as base editing. Using this tool, the team was able to identify specific nucleotides within T cells that influence immune cells’ response to stimuli, creating maps of DNA sequences and protein sites that are involved in human immune responses. The discoveries this project has facilitated could improve existing immunotherapies and reveal new drug targets for autoimmune diseases and cancer.

Senior author Alex Marson remarked: “our mapped sites provide insights into mutations found in patients with immune disorders. The enormous genetic dataset also works as a sort of cheat sheet, explaining biochemical code that will help us program future immunotherapies for cancer, autoimmunity, infections, and beyond.”

Read the paper  

complete yeast genomeResearchers are one step closer to synthesizing a complete yeast genome

A yeast strain with 31% synthetic DNA has been successfully produced, displaying normal morphology and budding behavior.

Supporting gut health

A diverse, good gut microbiome is important for human health. To support the gut, individuals can take a supplement called a probiotic, which is designed to boost the levels of beneficial live bacteria in the gut. Not only can they promote gut health, but probiotics can also support proper immune system function and enhance metabolism. A review published in September 2023 by researchers at Nanjing Agricultural University (China) highlighted how CRISPR-Cas can be used to tailor probiotics for specific health needs. For example, Escherichia coli (E. coli) can be modified using CRISPR-Cas9 to have probiotic qualities, killing antibiotic-resistant E.coli in the gut.

Senior author Nan Peng commented, “as important genome editing tools, CRISPR-Cas systems have opened the window to new improvements in genome editing dedicated to probiotics thanks to their high efficiency, flexibility, and specificity.”

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Mapping the fitness landscape of E. coliMapping the fitness landscape of E. coli

Escherichia coli may be more capable of becoming antibiotic resistant through evolution than previously thought.

Gene therapy for spinal muscular atrophy

Spinal muscular atrophy is a genetic disease caused by a loss-of-function mutation in the SMN1 gene, which leads to a reduced production of the survival motor neuron (SMN) protein. Using a CRISPR-based approach, researchers at Massachusetts General Hospital (MA, USA) have edited a similar gene to SMN1, termed SMN2, to be able to produce the survival motor neuron protein, which is essential for development and neuron function. This could potentially overcome the limitations of current gene therapy and small molecule treatments.

“By developing a single genome editing strategy to correct SMN2 to enable high levels of SMN protein expression, our approach could avoid the need to correct different types of mutations in the SMN1 gene,” commented senior author Benjamin Kleinstiver.

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organoidsBase editing for more efficient and representative organoids

Using base editing, researchers have been able to establish tumor organoids with multiple mutations more efficiently.

‘Cancer-shredding’ CRISPR technique

With yet another CRISPR-based research update, Gladstone Institutes present their ‘cancer-shredding’ CRISPR technique that can identify and eliminate repeating DNA sequences present in recurrent tumor cells while leaving healthy cells alone. This technique has shown promise against cell lines from a glioblastoma patient whose cancer returned after prior treatments.

“Glioblastoma is the most common lethal brain cancer, and patients still don’t have any good treatment options,” explained senior author Christof Fellmann. “Patients typically receive chemotherapy, radiation, and surgery, but most relapse in a matter of months. We wanted to find out if we could do something outside the box that could get around this problem of recurrence.” So far, the team’s CRISPR-based system is doing just that.

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T-cell therapiesNovel CRISPR-based screen identifies target for improved T-cell therapies

A team of researchers has identified a “master regulator” gene capable of improving T-cell therapies for treating cancer.

CRISPR-powered optothermal nanotweezers

Researchers have combined optothermal nanotweezers – tools that allow scientists to manipulate nanoparticles in situ – with CRISPR-based bio-detection, which has created a tool for identifying and manipulating bio-nanoparticles. These CRISPR-powered optothermal nanotweezers (CRONT) use optothermal induced diffusiophoretic force, turning the nanotweezers into a molecular probe for identifying bio-nanoparticles in situ.

The authors of the paper explained: “CRONT has enabled the immediate implementation of CRISPR-based biosensing within ultra-low detection volume. Optical tweezers are now endowed with DNA identification ability through the CRISPR-based biosensing system.”

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sgRNA efficiencyPredicting sgRNA efficiency with quantum biology and AI

Researchers advance understanding of single guide RNA (sgRNA) design to optimize CRISPR/Cas9 cutting efficiency using an explainable AI model.


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