Jun 13, 2019

Research deepens on using "jumping genes" in CRISPR therapy

Illustration: Rebecca Zisser/Axios

Two prominent teams of scientists recently announced transposons — or "jumping genes" — can improve the precision of CRISPR gene editing.

Why it matters: While this research is still in early stages, as both teams tested their techniques on bacterial cells, experts say the technique could allow edited genes to be more precisely inserted into genomes, possibly addressing concerns with current CRISPR systems that can lead to off-target editing and random deletions or even cancer.

Background: Transposons randomly jump from one site to the other, inserting genetic information as they go, using enzymes called transposases.

  • CRISPR tools currently use enzymes like Cas9 and Cas13 to cut and delete a portion of the genetic code, counting on the cell to use its repair function to glue the cut strands back together. That process sometimes introduces its own problems.
  • By combining the CRISPR tool with these transposons, which have the ability to easily introduce a large number of genes into cells, researchers hope to merge the best of both worlds, says Ilya Finkelstein, assistant professor at the University of Texas at Austin who was not part of either study.

Details: Both studies essentially combine CRISPR with different transposons and, in the process, unveil details about how natural CRISPR systems have evolved and why there are a diverse number of systems.

Study 1. CAST — This system, which stands for CRISPR-associated transposase, was published in Science last week by a team lead by the Broad Institute of MIT and Harvard University.

  • "This is filling a gap we couldn't address before, to able to insert DNA into the genome," study author Feng Zhang says of the ability to insert large genomes in a directed way.
  • They found the system, which uses a protein called Cas12K and Tn-7 transposes, produced the desired edit up to 80% of the time, which is higher than current CRISPR tools (roughly 20%). But, it also still had a number of off-target insertions.

Study 2. Cascade — This system was developed mainly by Columbia University and was published in Nature Wednesday.

  • Study author Sam Sternberg tells Axios, "Our discovery of RNA-guided integrases offers a fresh new approach, with the same programmability and ease of use as CRISPR–Cas9, but without the adverse effects associated with DNA breaks."
  • "Our system provides both the scissors and the glue, obviating the requirements for DNA breaks and host factors," Sternberg says.
  • This was found to produce the desired edit up to 60% of the time, but had fewer off-target insertions than the CAST system did, Sternberg adds.

What's next: Researchers plan to test the systems in plant and animals cells then want to see whether it can be used to treat some human diseases.

  • "There will be an explosion of transposon/CRISPR patents coming soon," Finkelstein predicts.

Meanwhile, pharmaceutical giant GlaxoSmithKline Thursday announced a collaboration called LGR with another prominent CRISPR scientist, Jennifer Doudna and UC Berkeley.

  • Doudna, who spoke at a press conference, says it's the "perfect marriage" to leverage the different strengths of the groups.
  • She says combining CRISPR technology to probe the underlying genomics of cells with machine learning and drug development technology will lead to new gene therapies.

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The wreckage of summer

Illustration: Sarah Grillo/Axios

We usually think of Memorial Day as the start of the summer, with all of the fun and relaxation that goes with it — but this one is just going to remind us of all of the plans that have been ruined by the coronavirus.

Why it matters: If you thought it was stressful to be locked down during the spring, just wait until everyone realizes that all the traditional summer activities we've been looking forward to are largely off-limits this year.

Coronavirus dashboard

Illustration: Aïda Amer/Axios

  1. Global: Total confirmed cases as of 3 a.m. ET: 5,410,228 — Total deaths: 345,105 — Total recoveries — 2,169,005Map.
  2. U.S.: Total confirmed cases as of 3 a.m. ET: 1,643,499 — Total deaths: 97,722 — Total recoveries: 366,736 — Total tested: 14,163,915Map.
  3. World: White House announces travel restrictions on Brazil, coronavirus hotspot in Southern Hemisphere Over 100 coronavirus cases in Germany tied to single day of church services — Boris Johnson backs top aide amid reports that he broke U.K. lockdown while exhibiting symptoms.
  4. Public health: Officials are urging Americans to wear masks headed into Memorial Day weekend Report finds "little evidence" coronavirus under control in most statesHurricanes, wildfires, the flu could strain COVID-19 response
  5. Economy: White House economic adviser Kevin Hassett says it's possible the unemployment rate could still be in double digits by November's election — Public employees brace for layoffs.
  6. Federal government: Trump attacks a Columbia University study that suggests earlier lockdown could have saved 36,000 American lives.
  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.

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Updated 4 hours ago - Politics & Policy

U.S. coronavirus updates

Data: The Center for Systems Science and Engineering at Johns Hopkins; Map: Andrew Witherspoon/Axios. This graphic includes "probable deaths" that New York City began reporting on April 14.

The CDC is warning of potentially "aggressive rodent behavior" amid a rise in reports of rat activity in several areas, as the animals search further for food while Americans stay home more during the coronavirus pandemic.

By the numbers: More than 97,700 people have died from COVID-19 and over 1.6 million have tested positive in the U.S. Over 366,700 Americans have recovered and more than 14.1 million tests have been conducted.