Figure 1: A: Structure of lipid
MC3. B: Structure of lipid SM-102. C: Structure of
When reviewing the approved structures
of MC3, SM-102, and ALC-0315 in these drugs/vaccines, it is apparent that
an ester-based biodegradable structure appears in all of them; the next most
commonly shared features are the multi/branched tail and unsaturated
structures. These structures help effectively facilitate RNA delivery by
enhancing membrane disruption, endosomal disruption, and RNA potency.
Although the FDA has approved ionizable
lipids for RNA delivery applications, there are still several challenges that
warrant further investigation and research. Firstly, the ionizable lipid is the
key LNP component that causes acute immune responses and long-term toxicity. Although
biodegradable ionizable lipids can be used to mitigate this issue,
premedication with glucocorticoids and anti-histamines before LNP infusion is
still needed. In order to overcome this challenge, optimization of linker
chemistry and anti-inflammatory properties through further investigation is
needed. Secondly, the preparation of ionizable lipids that have been rationally
designed is an extremely laborious synthesis process. To mitigate this issue,
investigation into combinatorial chemistry for simplified and accelerated
synthesis is needed. Among these two challenges are many more that show that
there are still vast opportunities for ionizable lipid optimization and
innovation to enable broader translation of RNA therapeutics.
Worldwide Lipid supplier
As a worldwide leading biochemical
supplier, BroadPharm offers a wide variety of novel Lipid molecules and customer service to empower our
clients’ advanced research in nanoparticle (NPL) drug delivery.
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