AUTHOR=Amoako Kagya , Mokhammad Amir , Malik Afrida , Yesudasan Sumith , Wheba Anas , Olagunju Oluwanifemi , Gu Sean X. , Yarovinsky Timur , Faustino Edward Vincent S. , Nguyen Juliane , Hwa John 

TITLE=Enhancing nucleic acid delivery by the integration of artificial intelligence into lipid nanoparticle formulation

JOURNAL=Frontiers in Medical Technology

VOLUME=Volume 7 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medical-technology/articles/10.3389/fmedt.2025.1591119

DOI=10.3389/fmedt.2025.1591119

ISSN=2673-3129

ABSTRACT=The advent of messenger RNA (mRNA) therapeutics has revolutionized medicine, with its potential underscored by rapid advancements during the COVID-19 pandemic. Despite its promise, nucleic acid delivery remains a formidable challenge due to enzymatic degradation, cellular uptake barriers, and endosomal trapping. Therapeutic lipid nanoparticles (LNPs), pioneered in the 1970s, have emerged as the gold standard for delivering mRNA and other nucleic acids, offering unparalleled advantages in stability, biocompatibility, and cellular targeting. This review explores the evolution and design of LNPs, focusing on their role in hematologic therapies and platelet transfection, where unique challenges arise due to platelets’ anucleate nature. The paper systematically evaluates the composition of LNPs, highlighting the role of ionizable, cationic, and neutral lipids in optimizing delivery efficiency, stability, and immune response modulation. Strategies to overcome platelet transfection barriers, including tailored lipid compositions and particle engineering, are discussed alongside advances in artificial intelligence (AI) for predictive nanoparticle design. Furthermore, it examines various nucleic acid cargoes, including mRNA, siRNA, and miRNA, and their therapeutic potential in addressing platelet-related disorders and advancing personalized medicine. Finally, the review delves into emerging technologies and the integration of AI to overcome existing barriers in nucleic acid delivery. By fostering interdisciplinary collaboration, this work aims to catalyze discoveries in LNP-based therapeutics and transformative advancements in hematologic treatments.