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In vivo targeted gene delivery using Adenovirus-antibody molecular glue conjugates

Rice-Boucher, P. J.; Kashentseva, E. A.; Dmitriev, I. P.; Guo, H.; Tremblay, J. M.; Shoemaker, C. B.; Curiel, D. T.; Lu, Z. H.

2025-02-01 bioengineering
10.1101/2025.01.31.635969 bioRxiv
Show abstract

Safe and efficient nucleic acid delivery to targeted cell populations remains a significant unmet need in the fields of cell and gene therapy. Towards this end, we pursued Adenoviral vectors genetically modified with the "DogTag" molecular glue peptide, which forms a spontaneous covalent bond with its partner protein, "DogCatcher". Genetic fusion of DogCatcher to single-domain or single-chain antibodies allowed covalent tethering of the antibody at defined locales on the vector capsid. This modification allowed simple, effective and exclusive targeting of the vector to cells bound by the linked antibody. This dramatically enhanced gene transfer into primary B and T cells in vitro and in vivo in mice. These studies form the basis of a novel method for targeting Adenovirus that is functional in stringent in vivo contexts and can be combined with additional well characterized Adenovirus modifications towards applications in cell engineering, gene therapy, vaccines, oncolytics, and others.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.