RNA therapy is a
disruptive technology comprising a rapidly expanding
category of drugs. Further translation of RNA therapies to the clinic
will improve the treatment of many diseases and help enable personalized
medicine. However, in vivo delivery of RNA remains challenging due
to the lack of appropriate delivery tools. Current state-of-the-art
carriers such as ionizable lipid nanoparticles still face significant
challenges, including frequent localization to clearance-associated
organs and limited (1–2%) endosomal escape. Thus, delivery
vehicles must be improved to further unlock the full potential of
RNA therapeutics. An emerging strategy is to modify existing or new
lipid nanocarriers by incorporating bioinspired design principles.
This method generally aims to improve tissue targeting, cellular uptake,
and endosomal escape, addressing some of the critical issues facing
the field. In this review, we introduce the different strategies for
creating bioinspired lipid-based RNA carriers and discuss the potential
implications of each strategy based on reported findings. These strategies
include incorporating naturally derived lipids into existing nanocarriers
and mimicking bioderived molecules, viruses, and exosomes. We evaluate
each strategy based on the critical factors required for delivery
vehicles to succeed. Finally, we point to areas of research that should
be furthered to enable the more successful rational design of lipid
nanocarriers for RNA delivery.
In 2018, LNPs enabled the first FDA approval of a siRNA drug (Onpattro); two years later, two SARS-CoV-2 vaccines (Comirnaty, Spikevax) based on LNPs containing mRNA also arrived at the...
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