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Compact gene editor enables efficient DNA editing in mice

Viral delivery of the editor in mice reduced a cholesterol-regulating protein by about 82% and LDL cholesterol by about 47%.

Paper by Yinghui Wei, Kun Xu, Yufei Liu, +14 more authorsZhaowei Wu · Northwest A&F University
Mouse livers beside a laboratory mouse, with sparse protein and cholesterol particles around the dark blue-green liver and dense particles around the gray…

Our read

Interventions
Studied:
Preprint: experiments in mice and mouse zygotes
What changed:
Circulating PCSK9 fell by about 82% after virus-based delivery of the editor in mice
The catch:
Circulating PCSK9 reduction is a proxy for DNA-editing efficiency

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Mouse zygotes—fertilized eggs at the one-cell stage—and mice were used in experiments testing PIVOT, a compact, RNA-guided DNA editor. The researchers engineered both the editing protein and its guide RNA to improve editing activity. PIVOT does not require the short DNA sequence beside a target that many other editors need.

Injection into mouse zygotes enabled germline editing, meaning changes that can pass to offspring. In mice, delivery using a single virus-based vector produced lasting disruption of the liver gene for PCSK9, a cholesterol-regulating protein. Circulating PCSK9 fell by about 82%, and LDL cholesterol fell by about 47%. The team also developed a stable, circular guide RNA that supported delivery using tiny fat-based particles.

Why it matters

For potential gene-editing approaches to age-related disease, reaching DNA targets and delivering the editor are practical hurdles. The work addresses both requirements for therapeutic use.

Caveats

The mouse experiments leave open how well the editor would work in people. The report is a preprint and has not been peer-reviewed.

Where the evidence stands

PCSK9

Cells: replicated by independent labs. Mice and humans: a single group. Worms or flies: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

No results posted: trials that ended over a year ago with no results on ClinicalTrials.gov and no paper reporting them.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 32 independent labs in 13 countries
  • 2 findings against
  • 166 trials, 11 with no results posted
  • Funders: Gouvernement du Canada | Canadian Institutes of Health Research and others
  • 7 of 46 findings with company ties
  • 153 of 166 trials sponsored by developers of drugs aimed at it

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