Base Editing Could Cure a Host of Genetic Diseases

Picture the familiar double helix of human DNA — a long, twisted ladder with 3 billion rungs on it, each made of a pair of genetic bases (A, T, C, and G). A mistake in just one base along that ladderan A where there should be a G — can be enough to cause a disease. In fact, researchers have linked over 31,000 different mistakes, known as “point mutations,” to human diseases. Now, an advanced form of gene therapy — called base editing — could make it possible to safely correct them.

Base editing is a type of gene editing technology, just like CRISPR. However, while CRISPR cuts through both strands of the DNA ladder to swap in different genes, a base editor makes precise changes to individual letters along the genome — a much less invasive kind of DNA surgery.

It’s like your spell-checker,” neuroscientist Jeffrey Holt said. “If you type the wrong letter, spell checker fixes it for you.” Base editing was first developed by Broad Institute researcher David Liu in 2016, and it’s not perfect — the best base editors still make off-target edits and aren’t 100%  efficient. However, the technique is more efficient than CRISPR and causes fewer errors, which has made it the focus of considerable research into correcting disease-causing point mutations.

Base editing is like your spell-checker. If you type the wrong letter, it fixes it for you,” explained Jeffrey Holt. Holt was part of a team that used base editing to partially restore the hearing of mice with a point mutation that causes deafness in people. Earlier in 2020, University of Illinois researchers used base editing to slow the progression of ALS in mice. More recently, Liu was part of a group that used base editing to correct the point mutation that causes progeria, a premature-aging syndrome, in mice. By changing a T to a C in a single gene, they were able to more than double the lifespan of mice with the disease.

There’s no guarantee that a therapy that works in mice will translate to humans (although gene editing is conceptually much simpler than drugs that rely on complex chemistry). To find out whether base editing can live up to its promise as a disease-curing technology, we need human studies — and now, one is just on the horizon.

On January 12, Massachusetts-based biotech company Verve Therapeutics announced the promising results of a study testing a base editing treatment for heterozygous familial hypercholesterolemia (HeFH), a genetic heart diseaseHeFH is fairly common, affecting about one in 500 people, and it causes consistently high levels of “badcholesterol (LDL-C) — that makes people with the disease susceptible to heart attacks or strokes at a relatively young age. In primates with HeFH, Verve used base editing to change an A to a G in a single gene. Within two weeks, the animals’ blood LDL-C levels had dropped by 59%. Six months later, they were still just as low.The treatment, dubbed “VERVE-101,” was well-tolerated, with no adverse effects reported.

When we started, we had no idea this would work,” Verve CEO Sekar Kathiresan said in a press release, adding, “It works, and we expect this to be durable for the lifetime of the animals.” Now, Verve wants to find out if VERVE-101 works in humans.

Source: https://www.freethink.com/

CRISPR-SKIP, New Gene Editing Technique

What if doctors could treat previously incurable genetic diseases caused by errors or mutations in genes? Thanks to new research by American scientists at the University of Illinois, we are one step closer to making that a reality. Published in Genome Biology, their work is based on CRISPR-Cas9, a groundbreaking genome editing system.

Typically, cells in the body “readDNA to produce the proteins needed for different biological functions. . Scientists can change how the DNA is read using CRISPR gene-editing technology. CRISPR-Cas9 is often used to cut out specific areas of DNA and repair faulty genes. In the current study, the researchers modified existing technology to create CRISPR-SKIP. Instead of breaking DNA to cut faulty genes out, CRISPR-SKIP changes a single base of the targeted DNA sequence, causing the cell to skip reading that section of DNA.

According to the study authors, CRISPR-SKIP can eliminate faulty sections of DNA permanently, allowing for long-lasting treatment of some genetic diseases with one treatment. They successfully tested their technique in cell lines from both mice and humans. The scientists aim to test the method in live organisms in the future.

CRISPR-SKIP has the potential to help treat many diseases such as cancer, rheumatoid arthritis, Huntington’s disease, and Duchenne muscular dystrophy to name a few. Because the method only requires editing of a single base, it is simple, precise, and adaptable to a variety of cell types and applications.

Source: https://news.illinois.edu/
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