Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

GENOME EDITING

Local magnetic activation of CRISPR

Nature Biomedical Engineering volume 3, pages 83–84 (2019)Cite this article

Subjects

Magnetic nanoparticles complexed with recombinant baculoviral vectors containing the CRISPR–Cas9 machinery enable the local magnetic activation of genome editing.

Clustered regularly interspaced short palindromic repeats (CRISPR)–Cas (CRISPR-associated protein) 9 exploits the Cas9 nuclease and a single-guide RNA (sgRNA) to edit genomes at predetermined loci. Because of CRISPR’s programmability and ease of use, CRISPR–Cas9 has been harnessed for in vivo genome editing to treat genetic disorders and infectious diseases1,2. However, efficient in vivo delivery of Cas9 and the sgRNA remains problematic, owing to challenges in the delivery of macromolecular complexes into cell nuclei in vivo. Also, Cas9 expression induces immune responses in vivo3, and humans can have pre-existing adaptive immunity to the Cas9 protein4. Hence, immune responses against Cas9 may attenuate the in vivo efficacy of CRISPR. Conversely, viral vectors, such as adeno-associated viruses (AAVs) and lentiviruses (LVs), are generally more effective than non-viral vectors at delivering the CRISPR macromolecules for in vivo genome editing5. However, the packaging capacity of these viral vectors is generally limited (~8 kb for LVs and ~4.7–5 kb for AAVs), hence impeding the incorporation of regulatory elements into them. Without appropriate regulation, Cas9 expression could last for weeks or even months, and could thus induce a high frequency of off-target effects. To avoid genotoxicity and to maximize therapeutic efficacy, a carrier with large packaging capacity and the ability to spatially control the expression of Cas9 in target tissue would be desirable. In this respect, Gang Bao and colleagues now report in Nature Biomedical Engineering that the complexing of magnetic nanoparticles (MNPs) and a recombinant baculovirus (BV) carrying the CRISPR–Cas9 macromolecules enables the spatial control of genome editing in target organs in mice6.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1: Spatial control of CRISPR–Cas9 genome editing via a nanomagnet.

References

  1. Komor, A. C., Badran, A. H. & Liu, D. R. Cell 168, 20–36 (2017).

    CAS  Article  Google Scholar 

  2. Ran, F. A. et al. Nature 520, 186–191 (2015).

    CAS  Article  Google Scholar 

  3. Chew, W. L. et al. Nat. Meth. 13, 868–874 (2016).

    CAS  Article  Google Scholar 

  4. Charlesworth, C. T. et al. Preprint at bioRxiv https://doi.org/10.1101/243345 (2018).

  5. Chen, X. & Goncalves, M. A. F. V. Mol. Ther. 24, 447–457 (2016).

    CAS  Article  Google Scholar 

  6. Zhu, H. et al. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-018-0318-7 (2019).

  7. Airenne, K. J. et al. Mol. Ther. 21, 739–749 (2013).

    CAS  Article  Google Scholar 

  8. Lin, M.-W. et al. Nucleic Acid. Res. 46, e93–e93 (2018).

    Article  Google Scholar 

  9. Sung, L.-Y. et al. Nat. Protoc. 9, 1882–1899 (2014).

    CAS  Article  Google Scholar 

  10. Lin, C.-Y. et al. Biomaterials 34, 9401–9412 (2013).

    CAS  Article  Google Scholar 

  11. Huser, A., Rudolph, M. & Hofmann, C. Nat. Biotechnol. 19, 451–455 (2001).

    CAS  Article  Google Scholar 

  12. Hwang, J. H. et al. Int. J. Pharm. 421, 397–404 (2011).

    CAS  Article  Google Scholar 

  13. Heun, Y. et al. Theranostics 7, 295–307 (2017).

    CAS  Article  Google Scholar 

  14. Nihongaki, Y., Kawano, F., Nakajima, T. & Sato, M. Nat. Biotechnol. 33, 755–760 (2015).

    CAS  Article  Google Scholar 

  15. Chen, C.-Y. et al. Mol. Pharmaceut. 8, 1505–1514 (2011).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan

    Mu-Nung Hsu & Yu-Chen Hu

  2. Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, Taiwan

    Yu-Chen Hu

Authors
  1. Mu-Nung Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu-Chen Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yu-Chen Hu.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hsu, MN., Hu, YC. Local magnetic activation of CRISPR. Nat Biomed Eng 3, 83–84 (2019). https://doi.org/10.1038/s41551-019-0354-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41551-019-0354-y

Further reading

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing