A team from the University of California, San Francisco, created a new electroporation-based CRISPR-Cas9 method, which eliminates viruses from the gene editing process and lays the groundwork for “safer, more precise and more efficient editing for CAR-T cancer treatments and other cell therapies,” reported FierceBiotech.1
As of now, virus-based editing is a time-consuming process in which genes are inserted into T-cell genomes. However, there is limited predictability. For example, producing viruses for cell therapies such as lentiviruses for Car-Ts, can take up to a year to produce.
A major barrier to the nonviral editing of T cells has been the “toxicity of the DNA sequences to be inserted into the target genome”.1Electroporation is a process that makes cell membranes more permeable for a temporary time. The process can be used to reduce toxicity allowing scientist to cut and paste specific sequences at the site of CRISPR programmed cut in the genome.1
UCLA’s Parker Institute for Cancer Immunotherapy worked alongside the team to replace a native receipt in human T cells with a different receptor engineered to find a specific subtype of melanoma cells. The modified targeted T cells attack the intended melanoma cells in a lab dish but leave the other types of cells unharmed.
With the virus-free CRISPR, the researchers were able to insert a longer piece of DNA into T cells than previously possible. Senior author Alexander Marson, M.D., Ph.D. said, “With the ability to rewrite long stretches of DNA—over 1,000 nucleotides at a time—we can start making more significant genetic changes to T-cells and make them more efficient at recognizing cancer and killing cancer.”1 To see more of the findings click here.
Future work includes makings the CAR-Ts safer by developing a safety switch. Furthermore, the electroporation method could be used for gene editing research targeted at inherited diseases.
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