Jan 24, 2019

A new enzyme could make human gene editing more precise

Performing a CRISPR-Cas9 process. Photo: Gregor Fischer/picture alliance via Getty Images

Scientists were able to alter an enzyme from a thermophilic bacteria so it can be used by CRISPR to edit human genes more effectively, per a study published in Nature Communications on Tuesday.

Why it matters: CRISPR is powerful but can sometimes cause large deletions or move DNA inadvertently. To make it more precise, researchers have been testing hundreds of new enzymes. Study author Feng Zhang says Cas12b's small size and precise targeting will enable it to be used for in vivo applications in primary human cells.

Background: The Cas12b family of enzymes was first brought to attention in 2015, and led to some recent studies (here and here) better defining their uses and limitations.

  • This study's enzyme, called BhCas12b, is from a bacterium (Bacillus hisashii) that lives in hot environments like geysers and volcanoes.
  • The main problem of using Cas12b was its temperature restriction. In its natural state, it's ineffective as a gene-editing tool at the lower body temperature of humans.

What they did: Zhang, who is a core institute member of the Broad Institute of MIT and Harvard, tells Axios that the team studied its three dimensional shape and made changes they predicted would make it more active at lower temperatures.

What they found: With the modifications and its naturally small size, BhCas12b was able to cut both DNA strands without many off-targets, Zhang says, and can efficiently edit genomes in primary human T cells.

"The size of the protein matters because for many applications, it needs to be packaged into a minimal viral vector for delivery. Viruses naturally have a restricted cargo capacity, so a smaller genome editing enzyme is beneficial."
— Feng Zhang

Outside perspective: Scientists not involved in this study say it shows Cas12b can be altered to become a promising CRISPR enzyme, but note that this small study should be validated with further research.

  • Ilya Finkelstein, assistant professor of molecular biology at the University of Texas-Austin, says he found it interesting they took a protein not normally functional in humans and engineered it to work. "There are hundreds of variants of these proteins. ... This suggests that the CRISPR toolkit will continue to grow."
  • Konstantin Severinov, principal investigator for Rutgers' Waksman Institute of Microbiology, says: "The study shows that Cas12b ... can be used, after some clever laboratory tweaking, for genomic editing in human cells. It may offer some advantages during editing compared to Cas9 and Cas12a."

Between the lines: Most CRISPR testing uses the first discovered enzyme, CAS9, so it's unlikely there will be a large shift to other enzymes soon, at least until they are proven to be safe and become cheaper.

  • "The one that is used by most people [Cas9] is not the best, it was simply the first to be characterised and reduced to practice. So there is clear room for improvement and many people are looking for better ones," Severinov says.
  • "[T]ime will tell whether Cas12b can take the crown from Cas9," Finkelstein adds.

Go deeper:

Go deeper

Coronavirus dashboard

Illustration: Aïda Amer/Axios

  1. Global: Total confirmed cases as of 4 p.m. ET: 5,463,392 — Total deaths: 344,503 — Total recoveries — 2,195,325Map.
  2. U.S.: Total confirmed cases as of 4 p.m. ET: 1,653,904 — Total deaths: 97,948 — Total recoveries: 366,736 — Total tested: 14,163,915Map.
  3. World: Italy reports lowest number of new cases since February — Ireland reports no new coronavirus deaths on Monday for the first time since March 21 — WHO suspends trial of hydroxychloroquine over safety concerns.
  4. 2020: Trump threatens to move Republican convention from North Carolina — Joe Biden makes first public appearance in two months.
  5. Public health: Officials are urging Americans to wear masks over Memorial Day.
  6. Economy: New York stock exchange to reopen its floor on Tuesday — White House economic adviser Kevin Hassett says it's possible the unemployment rate could still be in double digits by November's election — Charities refocus their efforts to fill gaps left by government.
  7. What should I do? Hydroxychloroquine questions answeredTraveling, asthma, dishes, disinfectants and being contagiousMasks, lending books and self-isolatingExercise, laundry, what counts as soap — Pets, moving and personal healthAnswers about the virus from Axios expertsWhat to know about social distancingHow to minimize your risk.
  8. Other resources: CDC on how to avoid the virus, what to do if you get it, the right mask to wear.

Subscribe to Mike Allen's Axios AM to follow our coronavirus coverage each morning from your inbox.

Updated 1 hour ago - Politics & Policy

Italy reports lowest number of new coronavirus cases since February

Italy’s aerobatic team Frecce Tricolori fly over Milan in Duomo Square on May 25. Photo: Francesco Prandoni/Getty Images

The Italian government reported 300 new cases of coronavirus on Monday, the lowest daily increase since Feb. 29.

Why it matters: Italy, the first country in Europe to implement a nationwide lockdown after emerging as a hotspot in March, appears to have finally weathered its coronavirus outbreak. Italy has reported nearly 33,000 total deaths, the third-highest total behind the U.S. and U.K.

Joe Biden makes first public appearance in over two months

Photo: Oliver Douliery/AFP via Getty Images

Former Vice President Joe Biden made his first in-person appearance in over two months on Monday to honor Memorial Day by laying a wreath at a Delaware veterans park, AP reports.

Why it matters: Biden, the Democratic Party's presumptive nominee, has taken the unprecedented step of campaigning from his home during the coronavirus pandemic, ever since canceling a rally in Cleveland on March 10.