Development of a high-throughput platform for screening lipid nanoparticles for mRNA delivery.
Nanoscale
; 14(4): 1480-1491, 2022 Jan 27.
Article
in English
| MEDLINE | ID: covidwho-1621289
ABSTRACT
mRNA lipid nanoparticles (LNPs) are at the forefront of nucleic acid intracellular delivery, as exemplified by the recent emergency approval of two mRNA LNP-based COVID-19 vaccines. The success of an LNP product largely depends on the systematic optimisation of the four lipidic components, namely the ionisable lipid, PEG lipid, structural and helper lipids. However, the in vitro screening of novel lipidic components and LNP compositions is limited by the low-throughput of LNP preparation. To address these issues, we herein present an automated high-throughput screening platform to select novel ionisable lipids and corresponding LNPs encapsulating mRNA in vitro. This high-throughput platform employs a lab-based automated liquid handling system, amenable to high-throughput (up to 384 formulations per plate and several plates per run) and allows precise mixing and reproducible mRNA LNP preparation which ensures a direct head-to-head comparison of hundreds and even thousands of novel LNPs. Most importantly, the robotic process has been successfully applied to the screening of novel LNPs encapsulating mRNA and has identified the same novel mRNA LNP leads as those from microfluidics-mixing technology, with a correlation coefficient of 0.8751. This high-throughput platform can facilitate to narrow down the number of novel ionisable lipids to be evaluated in vivo. Moreover, this platform has been integrated into a fully-automated workflow for LNP property control, physicochemical characterisation and biological evaluation. The high-throughput platform may accelerate proprietary lipid development, mRNA LNP lead optimisation and candidate selection to advance preclinical mRNA LNP development to meet urgent global needs.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Vaccines, Synthetic
/
Nanoparticles
/
COVID-19 Vaccines
/
COVID-19
/
MRNA Vaccines
Type of study:
Experimental Studies
/
Systematic review/Meta Analysis
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
Nanoscale
Year:
2022
Document Type:
Article
Affiliation country:
D1nr06858j
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