-functionalized may enable more selective mRNA delivery to CD4+ T cells.
Evidence
This formulation and platform experiment tested SM102 or MC3 lipid nanoparticles conjugated to validated and AI-designed CD4-binding aptamers for binding, transfection, biodistribution, and safety in recombinant, cell, and in vivo systems.
Caveat
The abstract reports platform performance rather than therapeutic efficacy, and the text is partly garbled, limiting confidence in some experimental details.
Simplified
genetic engineering of T cells could overcome the logistical, biological, and safety challenges ofmodification, but effective and safe delivery systems remain limited by a lack of cellular specificity. Here, we developed -functionalized (LNPs) for targeted mRNA delivery to CD4 + T cells, employing both a validated CD4-binding aptamer (Apt62) and novel aptamers generated using our proprietary transformer-based AI language model, AptaBLE. LNPs formulated with ionizable lipid SM102 or MC3 and conjugated with aptamers at controlled densities were physiochemically characterized and assessed for binding,transfection,biodistribution, and safety evaluation. Aptamer-functionalized LNPs demonstrated selective nanomolar binding to recombinant CD4, achieved enhanced transfection of CD4⁺ versus CD4T cells, and significantly enriched mRNA delivery to immune-rich tissues, achieving up to 70-fold spleen signal enhancement with SM102 formulations Compared to non-targeted controls, while maintaining suitable safety profiles. Overall, these findings demonstrate aptamer-functionalized LNPs, augmented by AI-guided aptamer design, as a tunable, non-immunogenic platform forT-cell engineering. In vivo ex vivo in vitro in vivo in vitro in vivo in vivo -
Key numbers
70-fold
Increase in Spleen Signal
Spleen signal enhancement compared to non-targeted controls.
100:1
Transfection Efficiency in CD4⁺ T Cells
Apt62 conjugation at a ratio of 100 per LNP.
Full Text
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A patent application related to this work has been filed by Atom Bioworks (Application No. 19/272,758), listing S.S., M.R., A.F., and S.Y. as inventors. S.Y. is a co-founder of Atom Bioworks. S.S. and M.R. are employees of Atom Bioworks. K.F. serves as a Science Advisor to Atom Bioworks. A.D. declares no competing interests.
