New gene-writing technology to develop more effective and safe therapies

New gene writing technology developed to provide more effective and safer therapies

From left to right: Marc Güell, Dimitrije Ivančić, Avencia Sánchez-Mejías and Maria Pallarès. Credit: UPF

An international, multidisciplinary research team from the Translational Synthetic Biology Laboratory at Pompeu Fabra University (Barcelona, Spain) led by Dr. Marc Güell has an article in the journal. released Nature communication Demonstrates the potential of Find, Cut and Transfer (FiCAT) technology as a cutting edge gene writing tool to develop advanced therapies that are safer and more effective with few treatments for future clinical use in patients with genetic and oncological diseases Options.

The UPF Translational Synthetic Biology Laboratory has been working on gene editing and synthetic biology applied to gene therapy since 2017. FiCAT technology is a major scientific breakthrough in overcoming the current limitations of the technology used today for genome editing and Gene therapy.

“Human genome engineering has made significant strides in the last decade with the development of new editing tools, but there was still a technological gap, the therapeutic one Genes can be efficiently transferred with few size restrictions, “says Dr. Marc Güell, supervisor of the study.

In this work, the researchers developed an efficient and precisely programmable gene writing technology based on the combination of the modified proteins CRISPR-cas and the piggy Bac transposase (PB) for inserting small and large fragments. Dr. Maria Pallarès, co-first author of the study, says: “CRISPR is characterized by its precision in processing small fragments. However, transposases allow us to insert large fragments in an uncontrolled manner. We have combined the best of each technology. ”

“In this way, FiCAT technology enables us to insert large DNA fragments precisely into the genome. This enables us to develop therapeutic solutions for currently untreated diseases such as Duchenne. ” muscular dystrophy, or some cases of hereditary blindness where the affected gene is large, “says Dr. Avencia Sánchez-Mejías, lead researcher of the group and co-supervisor of the work.

They tested the technology in human and mouse cell lines, achieved efficiencies of 5 to 22 percent with minimal off-target insertions, and demonstrated on-target gene transfer in vivo in mouse liver and germline cells in mouse models. Finally, they carried out a targeted further development of FiCAT and further improved efficiency by 25 to 30 percent. “We gradually modified enzymes so that they got the function we were looking for and selected those that functioned better,” says Dimitrije Ivančić, co-first author of the article. “Our work is a clear example that enzyme engineering has great potential in the context of genome editing,” he concludes.

Genome editing for the treatment of human retinal degeneration

More information:
Maria Pallarès-Masmitjà et al., Find and Cut-and-Transfer (FiCAT) Mammalian Genome Engineering, Nature communication (2021). DOI: 10.1038 / s41467-021-27183-x

Provided by the University of Pompeu Fabra – Barcelona

Quote: New gene writing technology to develop more effective and safer therapies (2021, December 14), accessed on December 14, 2021 from safe therapies. html

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