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
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
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

References
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.
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.
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.
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.
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.
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).
Rights and permissions
About this article
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
Published:
DOI: https://doi.org/10.1038/s41587-023-01819-3