Evidence map›Paper›PMID 35866031›Full record

ReviewFrontiers in bioengineering and biotechnology2022

Programmable RNA-Guided Large DNA Transgenesis by CRISPR/Cas9 and Site-Specific Integrase Bxb1.

Vishnu Hosur, Benjamin E Low, Michael V Wiles

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in bioengineering and biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Gene-targeted therapies: Overview and implications.American journal of medical genetics. Part C, Seminars in medical genetics · 2023
    Article
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Vishnu HosurThe Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, United States.
Benjamin E LowThe Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, United States.
Michael V WilesThe Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, United States.
Jackson Laboratory · US

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI William Carl Skarnes · 1985 to 2026
$61.9M
Site-specific Integration of Large (10-100 kb) DNA Constructs into the Mouse Genome and Human Induced Pluripotent Stem Cells Using the Cas9-Bxb1 Integrase ToolboxR01CA265978 · NCI · JACKSON LABORATORY · PI Vishnu Hosur · 2022 to 2026
$3.2M
Development and Validation of a Novel Cas13a and Nanoparticle Guide-RNA Delivery System that Allows Precise Ablation of Host Macrophage Populations in a Humanized Mouse ModelR21OD027052 · OD · JACKSON LABORATORY · PI WILES, MICHAEL VAN · 2019 to 2020
$480k
NCI NIH HHS P30 CA034196NCI NIH HHS R01 CA265978NIH HHS R21 OD027052
6 · The paper itself

Abstract

The inability to insert large DNA constructs into the genome efficiently and precisely is a key challenge in genomic engineering. Random transgenesis, which is widely used, lacks precision, and comes with a slew of drawbacks. Lentiviral and adeno-associated viral methods are plagued by, respectively, DNA toxicity and a payload capacity of less than 5 kb. Homology-directed repair (HDR) techniques based on CRISPR-Cas9 can be effective, but only in the 1-5 kb range. In addition, long homology arms-DNA sequences that permit construct insertion-of lengths ranging from 0.5 to 5 kb are required by currently known HDR-based techniques. A potential new method that uses Cas9-guided transposases to insert DNA structures up to 10 kb in length works well in bacteria, but only in bacteria. Surmounting these roadblocks, a new toolkit has recently been developed that combines RNA-guided Cas9 and the site-specific integrase Bxb1 to integrate DNA constructs ranging in length from 5 to 43 kb into mouse zygotes with germline transmission and into human cells. This ground-breaking toolkit will give researchers a valuable resource for developing novel, urgently needed mouse and human induced pluripotent stem cell (hiPSC) models of cancer and other genetic diseases, as well as therapeutic gene integration and biopharmaceutical applications, such as the development of stable cell lines to produce therapeutic protein products.

Indexed as

Bxb1 integraseCas9prime editingrecombinasetransgenesis

Identifiers

PMID35866031
PMCPMC9294445
OpenAlexW4284678889

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.