Programmable Surface Receptor-Mediated Cell Targeting with Designer Antibody-Routed Nanoparticles (DARTs)
- 1Stanford University
Abstract
Precise in vivo delivery remains a massive barrier to therapeutic genome editing. Recently, major strides have been made towards cell type-specific delivery, with potential to improve the safety profiles of future gene therapies. However, programming such targeted tropism is limited by the minimal repertoire of scFv sequences, nanobodies, and viral fusogens that enable cell-type specificity, and the slow, iterative design-build-test cycle required to identify and optimize them. Here, we overcome this bottleneck by developing the designer antibody-routed (DART) platform: a modular, plug-and-play tool that decouples delivery vehicle production from tropism engineering. By presenting generic, bioorthogonal antibody-binding interfaces on the surfaces of enveloped particles, the DART system enables conjugation of those particles with off-the-shelf antibodies that direct cell entry without requiring genetic or chemical manipulation. Designer antibody-routed virus-like particles (DARTs) leverage this facile conjugation method to interrogate and identify transduction-competent surface antigens across cell types. They enable combinatorial targeting and the discovery of antigens that synergistically enhance transduction. Finally, DARTs function in the fetal murine nervous system, empirically identifying CD56 as a previously uncharacterized surface antigen enabling editing in hard-to-transduce neural populations. Overall, the DART platform provides a universal tool for rapidly profiling unique, targetable antigens and leveraging them for precision editing applications.
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BibTeX
@misc{roth2026programmable,
title = {{Programmable Surface Receptor-Mediated Cell Targeting with Designer Antibody-Routed Nanoparticles (DARTs)}},
author = {G. V. Roth and I. R. Gengaro and N. Ahmadian and K. Gao and D. Wang and S. Xu and M. Chavez and P. Finn and A. Wang and L. S. Qi},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.18.757718},
url = {https://www.biorxiv.org/content/10.64898/2026.10.18.757718v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Programmable Surface Receptor-Mediated Cell Targeting with Designer Antibody-Routed Nanoparticles (DARTs)
AU - G. V. Roth
AU - I. R. Gengaro
AU - N. Ahmadian
AU - K. Gao
AU - D. Wang
AU - S. Xu
AU - M. Chavez
AU - P. Finn
AU - A. Wang
AU - L. S. Qi
PY - 2026
DA - 2026/10/18
PB - bioRxiv
DO - 10.64898/2026.10.18.757718
UR - https://www.biorxiv.org/content/10.64898/2026.10.18.757718v1
AB - Precise in vivo delivery remains a massive barrier to therapeutic genome editing. Recently, major strides have been made towards cell type-specific delivery, with potential to improve the safety profiles of future gene therapies. However, programming such targeted tropism is limited by the minimal repertoire of scFv sequences, nanobodies, and viral fusogens that enable cell-type specificity, and the slow, iterative design-build-test cycle required to identify and optimize them. Here, we overcome this bottleneck by developing the designer antibody-routed (DART) platform: a modular, plug-and-play tool that decouples delivery vehicle production from tropism engineering. By presenting generic, bioorthogonal antibody-binding interfaces on the surfaces of enveloped particles, the DART system enables conjugation of those particles with off-the-shelf antibodies that direct cell entry without requiring genetic or chemical manipulation. Designer antibody-routed virus-like particles (DARTs) leverage this facile conjugation method to interrogate and identify transduction-competent surface antigens across cell types. They enable combinatorial targeting and the discovery of antigens that synergistically enhance transduction. Finally, DARTs function in the fetal murine nervous system, empirically identifying CD56 as a previously uncharacterized surface antigen enabling editing in hard-to-transduce neural populations. Overall, the DART platform provides a universal tool for rapidly profiling unique, targetable antigens and leveraging them for precision editing applications.
ER -