Targeted delivery of diverse biomolecules with engineered bacterial nanosyringes

Nat Biotechnol. 2025 Aug 12. doi: 10.1038/s41587-025-02774-x.

Joseph Kreitz ¹ ² ³ ⁴ ⁵ ⁶ ⁷, Victoria Yang ¹ ² ³ ⁴ ⁵ ⁶ ⁷, Mirco J Friedrich ¹ ² ³ ⁴ ⁵ ⁶ ⁷, Julie Pham ¹ ² ³ ⁴ ⁵ ⁶ ⁷, Rhiannon K Macrae ¹ ² ³ ⁴ ⁵ ⁶ ⁷, Feng Zhang ⁸ ⁹ ¹⁰ ¹¹ ¹² ¹³ ¹⁴

Affiliations

1 Howard Hughes Medical Institute, Cambridge, MA, USA.
2 Yang Tan Collective, Cambridge, MA, USA.
3 McGovern Institute for Brain Research at MIT, Cambridge, MA, USA.
4 Broad Institute of MIT and Harvard, Cambridge, MA, USA.
5 Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
6 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
7 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
8 Howard Hughes Medical Institute, Cambridge, MA, USA. zhang@broadinstitute.org.
9 Yang Tan Collective, Cambridge, MA, USA. zhang@broadinstitute.org.
10 McGovern Institute for Brain Research at MIT, Cambridge, MA, USA. zhang@broadinstitute.org.
11 Broad Institute of MIT and Harvard, Cambridge, MA, USA. zhang@broadinstitute.org.
12 Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA, USA. zhang@broadinstitute.org.
13 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. zhang@broadinstitute.org.
14 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. zhang@broadinstitute.org.

PMID: 40796978 DOI: 10.1038/s41587-025-02774-x

Abstract

The Photorhabdus virulence cassette is a microbial nanosyringe that can be engineered to deliver protein cargos into human cells. Here we further modify this system to incorporate exogenous cargos and targeting moieties in vitro. We show that this method, termed SPEAR, enables loading of different types of cargo (including folded ribonucleoproteins and single-stranded DNA) and targeting of defined cell types both in vitro and in vivo.

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Protease Inhibitor Cocktail (EDTA-Free, 100× in DMSO)

Protease Inhibitor Cocktail

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