New Gene-Editing Tools Aim to Fight Disease

Scientists have developed genetic tools that help solve two of the problems hampering genome-editing superweapon CRISPR.

These discoveries provide new hope for treating, or even curing, certain genetic diseases.

The first is led by Harvard biochemist David Liu, who last year invented a method of switching single letters in the 3-billion-letter human genome to repair disease-causing mutations.

While CRISPR/Cas9 simply cuts out existing genes, Liu and his team established a base editor that can rearrange the sequences of our genetic code—like a master forger fooling even the most adept experts.

Their adenine base editor, or ABE for short, can neatly turn the DNA letter A (adenine) into G (guanine) “with surprising efficiency” and “virtually no” collateral damage, according to a Harvard press announcement.

Harvard and Broad Institute researchers developed a DNA base editor that could one day be used to treat many common genetic diseases (via Susannah Hamilton/Harvard University)

“What we’ve developed is a base editor, a molecular machine, that in a programmable, irreversible, efficient, and extremely clean way can correct … mutations in the genome of living cells,” Liu said in a statement.

The entire family of base-editing systems developed in Liu’s lab can now correct all so-called “transition” mutations—C to T, T to C, A to G, G to A—which account for nearly two-thirds of genetic conditions, including sickle-cell anemia, cystic fibrosis, Tay-Sachs disease, and color blindness.

“Creating a machine that makes the genetic change you need to treat a disease is an important step forward, but it’s only one part of what’s needed to treat a patient,” the Harvard professor said. “We still have to deliver that machine, we have to test its safety, we have to assess its beneficial effects in animals and patients and weigh them against any side effects.

In a separate study, published in the journal Science, Feng Zhang of the Broad Institute describes a new version of CRISPR that can efficiently edit RNA, the single-stranded cousin of DNA.

The system—RNA Editing for Programmable A to I Replacement (REPAIR)—can reverse disease-causing mutations at the RNA level, and provide other therapeutic and basic science applications.

“The ability to correct disease-curing mutations is one of the primary goals of genome editing,” according to Zhang, a professor in the departments of brain and cognitive science and biological engineering at MIT.

“So far, we’ve gotten very good at inactivating genes, but actually recovering lost protein function is much more challenging,” he said. “This new ability to edit RNA opens up more potential opportunities to recover that function and treat many diseases, in almost any kind of cell.”

A new REPAIR system edits RNA, rather than DNA (via Susanna Hamilton/Broad Communications)

Like ABE, REPAIR can target individual RNA letters and reverse the impact of pathogenic G-to-A mutation, which may cause focal epilepsy, Duchenne muscular dystrophy, and Parkinson’s disease.

“REPAIR can fix mutations without tampering with the genome, and because RNA naturally degrades, it’s a potentially reversible fix,” co-author David Cox, a graduate student in Zhang’s lab, explained.

Source: geek