Selection by essential-gene exon knock-in for the generation of efficient cell therapies

Selection by essential-gene exon knock-in for the generation of efficient cell therapies

By linking transgene expression with that of a housekeeping gene, SLEEK (selection by essential-gene exon knock-in) enables efficient knock-in of complex cargos in a variety of clinically relevant cell types. Using SLEEK, we were able to substantially improve the tumor suppression ability and in vivo persistence of a cell therapy.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

209,00 € per year

only 17,42 € per issue

Rent or buy this article

Get just this article for as long as you need it

$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: SLEEK achieves high transgene knock-in efficiency.

References

  1. Wilkinson, A. C., Igarashi, K. J. & Nakauchi, H. Haematopoietic stem cell self-renewal in vivo and ex vivo. Nat. Rev. Genet. 21, 541–554 (2020). This review article highlights the opportunities for cell therapies applied to hemoglobinopathies.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  2. Bailey, S. R. & Maus, M. V. Gene editing for immune cell therapies. Nat. Biotechnol. 37, 1425–1434 (2019). This review article presents the synchrony between gene editing and cell therapies.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  3. Zhang, L. et al. AsCas12a ultra nuclease facilitates the rapid generation of therapeutic cell medicines. Nat. Commun. 12, 3908 (2021). This paper reports the use of a high-specificity AsCas12a enzyme.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  4. Kao, T. et al. GAPTrap: a simple expression system for pluripotent stem cells and their derivatives. Stem Cell Rep. 7, 518–526 (2016). This paper reports the GAPDH site as a reliable site for gene expression in iPSCs.

    Article 
    CAS 

    Google Scholar
     

  5. Ho, J. Y. et al. Promoter usage regulating the surface density of CAR molecules may modulate the kinetics of CAR-T cells in vivo. Mol. Ther. Methods Clin. Dev. 21, 237–246 (2021). This paper demonstrates the differential CAR responses using different promoters.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Allen, A. G. et al. A highly efficient transgene knock-in technology in clinically relevant cell types. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-01779-8 (2023).

About this article

Verify currency and authenticity via CrossMark

Cite this article

Selection by essential-gene exon knock-in for the generation of efficient cell therapies.
Nat Biotechnol (2023). https://doi.org/10.1038/s41587-023-01819-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1038/s41587-023-01819-3

Read More

Leave a Reply

Your email address will not be published.