CRISPR Enhances Gene Therapy to Fight Inherited Diseases


Source: Washington University School of Medicine in St. Louis

Summary: Researchers have combined the gene-editing tool CRISPR with a deactivated virus to deliver a healthy gene to a precise location in the bodies of living mice.


For decades, scientists have studied viruses for their potential to deliver genes directly into cells. After all, the common cold and other illnesses result when viruses infect cells and insert harmful DNA. To accomplish gene therapy, scientists have exploited this function of viruses, rendering them harmless and enabling them instead to deliver healthy genes to counteract disease. Gene therapy has shown promise in treating inherited genetic diseases, but a major issue that has frustrated scientists remains: Replacing a “bad” gene with a healthy one often is a short-lived fix. Researchers from the Washington University School of Medicine have combined the gene-editing tool CRISPR with a deactivated virus to deliver a healthy gene to a precise location in the bodies of living mice. More importantly, they demonstrated that the inserted gene remained properly activated in mice for at least 6 months. The study findings were published in the journal Gene Therapy.

Gene Therapy

Shown is a transmission electron microscope image of adenovirus particles. A new study, in mice, combined molecular tools — adenovirus and CRISPR — to improve gene therapy. Credit: CDC/G. William Gary Jr

The typical duration for this type of gene expression is four to six weeks, according to the team. But the advent of CRISPR gene-editing technology has changed that. While not perfect, CRISPR is a precise method to edit the genome and is user-friendly compared with other precision gene-editing techniques. It has been compared, for example, to the “find and replace” function of a word processor. Scientists tell CRISPR what combination of DNA “letters” to look for in a cell and what sequence of DNA to replace them with or to insert into that location. The challenge with CRISPR is delivering it to the right place inside the body. To maximize efficiency and longevity, the team used adenovirus (causes the common cold) as the delivery vehicle. The mice in this study appeared to be healthy for the duration of the experiment, but questions remain about the possibility of adenovirus, and perhaps the CRISPR protein machinery, triggering an immune response.

Prof. David T. Curiel said, “We targeted these viruses with CRISPR to a part of the genome that’s called a safe harbor”, “These are parts of the DNA sequence that are quiet, removed from more active areas, and where it’s unlikely for this type of editing to do anything harmful.”


More Information: Calvin J. Stephens et al, “Targeted in vivo knock-in of human alpha-1-antitrypsin cDNA using adenoviral delivery of CRISPR/Cas9”, Gene Therapy (2018) DOI: 10.1038/s41434-018-0003-1 


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