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Utilizing Grab Antibody as a Targeting Module in mRNA-LNP Platforms
Abstract No. : 71

Category

Advanced biomaterials and platform technology
Messenger RNA-lipid nanoparticles (mRNA@LNPs) constitute a highly effective platform for administering therapeutic messenger RNA to previously undruggable targets. However, conventional antibody functionalization methods, which depend on chemical conjugation, are often labor-intensive and yield heterogeneous nanoparticles with improperly oriented antibodies, ultimately compromising targeting accuracy and delivery performance. In order to address these challenges, we developed a chemical-free methodology inspired by the formation of a natural protein corona. By engineering a fusion of apolipoprotein with the Fc domain of a targeting antibody, we facilitated spontaneous, correctly oriented antibody assembly onto mRNA@LNPs without altering the lipid nanoparticle formulation workflow or employing complex conjugation steps. This approach preserved nanoparticle stability while significantly enhancing targeting precision. We demonstrated its efficacy utilizing trastuzumab-functionalized mRNA@LNPs, which selectively delivered messenger RNA to HER2-overexpressing cancer cells and achieved robust protein expression. Importantly, in contrast to non-targeted LNP controls, the trastuzumab-modified LNPs exhibited no systemic toxicity. Furthermore, the targeted delivery of p53 tumor suppressor messenger RNA through this platform resulted in complete tumor regression, underscoring strong antitumor efficacy. This streamlined, scalable, and adaptable strategy for antibody functionalization substantially improves the targeted delivery and therapeutic precision of mRNA@LNPs, presenting extensive potential for advancing gene therapy applications.
#Grab Antibody
#Lipid Nanoparticle
#Apolipoprotein
#Targeted Delivery
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