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We present a class of programmable polymer nanoparticles capable of intravenous pDNA delivery with ∼350 000-fold enhancement of specificity to the lung by qPCR in mice. Molecular level insight of these polyelectrolytes is connected to bioperformance, exemplifying how robust, data-driven workflows can expedite synthesis/screening campaigns for gene therapy.

Graphical abstract: Predictive design of multimonomeric polyelectrolytes enables lung-specific gene delivery

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