CRISPR-Cas9: Gene Therapy 2.0 Is on Its Way!

Gene therapy is emerging as a therapeutic option for a rising range of diseases three decades after its first introduction. Researchers have created therapies for a variety of blood diseases, as well as degenerative eye and muscular diseases, by developing new ways to fix or modify the way genes work.

The original gene therapy strategies, some of which are still being used today, are based on a simple concept: delivering a functional copy of the gene into affected cells when the disease is caused by a missing or defective gene.

This idea, says Prashant Mali, a bioengineer from the University of California, San Diego, was the "version 1.0 definition of gene therapy."

In 1990, researchers at the National Institutes of Health (NIH) treated two young girls with severe immunodeficiency caused by a missing enzyme, which was one of the first efforts of gene therapy. The NIH scientists isolated white blood cells from the girls' blood, which were then "infected" with viruses carrying the gene for the missing enzyme. The scientists then injected the girls with the corrected cells. The treatment didn't cure them, but it did deaden some symptoms and showed that the method could be employed safely.

A rush of other gene therapy studies followed, but in 1999, 18-year-old Jesse Gelsinger died after his immune system went into overdrive as a result of an experimental gene treatment aimed to cure his metabolic liver disease. Then in 2003, several persons treated for immunodeficiency got leukemias, which is an unfortunate result of the virus randomly inserting its cargo into cancer-promoting regions of the genome.

Then, for a decade, gene therapy came to a halt. With clinical trials stopped, scientists returned to the lab to study and modify viral vectors. By deleting extra genes and treating them with chemicals they tried to make the therapy safer and more effective at reaching target cells.

Researchers in Pennsylvania and Maryland separately announced findings from studies for the treatment of leukemia and lymphoma in the early 2010s, giving gene therapy a second chance. The experimental therapy boosted the immune systems of the patients, allowing them to recognize and eliminate cancer cells.

Technology has ushered in a new age in the last decade, and the concept of gene therapy is still evolving. The most recent techniques avoid delivering healthy genes, and are for precisely repairing the gene within the cell. The issue now is whether we could truly go in and correct a mutation or other problem in the DNA.

This innovation is enhanced by the Nobel Prize–winning discovery of CRISPR-Cas9, an immune defense system in bacteria that can detect specific DNA sequences of invading viruses and direct an enzyme to slice up and destroy the viral genome. Scientists found they could use it to make precise cuts within the mammalian genome. In just seven years the technique has moved from lab experiments in mammalian cells to human trials.

The cargo in CRISPR-based therapies is not a piece of DNA but the gene-editing system itself, introduced into cells either by a virus, within a nanoparticle, or on its own as an RNA-protein complex, as introduced by an expert from Creative Biolabs, who is professional in gene editing for gene therapy. The therapies can be used ex vivo to alter cells in the lab before returning them to the patient or by sending gene-editing tools directly to affected tissues, where they edit cellular genomes.

New methods have enabled researchers to achieve greater accuracy and delicacy, allowing them to aim even higher. Until now, treatments for neurological ailments, autoimmune disorders, and other malignancies are being developed.

With gene treatments successfully alleviating some illnesses, researchers, clinicians, and patients are hoping to sustain the progress of the past decade and establish gene therapy as a cornerstone of modern medicine.

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