- Research Briefing
- Published:
Nature Biotechnology (2026) Cite this article
-
247 Accesses
-
3 Altmetric
Engineering complex phenotypes into mammalian cells holds profound potential but remains a largely intractable engineering challenge. We developed shotgun genetic engineering (SGE), a multiplexed strategy that screens millions of combinatorial solutions in a single experiment. This approach uses selection strategies that reveal effective designs, facilitating rapid engineering of complex biological functions.
This is a preview of subscription content, access via your institution
Access options
Access through your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$32.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to the full article PDF.
USD 39.95
Prices may be subject to local taxes which are calculated during checkout
Subjects
References
-
Lim, W. A. The emerging era of cell engineering: harnessing the modularity of cells to program complex biological function. Science 378, 848–852 (2022). This review article outlines potential therapeutic applications of cellular engineering.
-
Nielsen, J. & Kiesling, J. Engineering cellular metabolism. Cell 164, 1185–1197 (2016). This review article outlines to our knowledge of cellular metabolism, how they impede metabolic engineering efforts, and how they are addressed using the DBT framework.
-
Srinivasan, P. & Smolke, C. D. Biosynthesis of medicinal tropane alkaloids in yeast. Nature 585, 614–619 https://doi.org/10.1038/s41586-020-2650-9 (2020). This article describes metabolic engineering feat in yeast: the successful biosynthesis of medicinal tropane alkaloids by overexpression of 26 genes across six subcellular locations.
-
Rai, K. et al. Ultra-high-throughput mapping of genetic design space. Nature 650, 1035–1044 (2026). This paper describes the CLASSIC method for optimizing gene circuit designs.
-
Trolle, J. et al. Resurrecting essential amino acid biosynthesis in mammalian cells. eLife 11, e72847 (2022). This paper features our previous work to engineer valine biosynthesis in CHO cells.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Trolle, J. et al. Highly multiplexed mammalian metabolic engineering with a shotgun approach. Nat. Biotechnol. https://doi.org/10.1038/s41587-026-03318-7 (2026).
Rights and permissions
About this article
Cite this article
High-throughput metabolic engineering in mammalian cells. Nat Biotechnol (2026). https://doi.org/10.1038/s41587-026-03317-8
-
Published:
-
Version of record:
-
DOI: https://doi.org/10.1038/s41587-026-03317-8