DeepDelivery identifies human proteins for mRNA delivery

The platform screened the proteome and nominated 512 candidate proteins. Experimental validation confirmed that 12 of the 15 selected human proteins functioned effectively as scaffold components, facilitating particle formation and mRNA delivery. The study highlights that several tripartite motif (TRIM) family proteins, typically linked to antiviral responses, showed strong assembly and delivery activity.

Using model interpretability and perturbation analyses, the team identified specific TRIM domain features that influenced prediction scores. These insights guided the engineering of TRIM25-specific domains to improve delivery efficiency. The work establishes a framework for mining the human proteome for scaffold components in programmable mRNA delivery systems. The research was supported by various Chinese national and regional funding bodies, and the authors have filed patent applications for the discovered scaffold proteins.