SM-102 is a synthetic amino

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids incl ...

which is used in combination with other lipids to form

lipid nanoparticle lipid nanoparticles (LNPs), are nanoparticles composed of lipids. They are a novel pharmaceutical drug delivery system (and part of nanoparticle drug delivery), and a novel pharmaceutical formulation. LNPs as a drug delivery vehicle were f ...

s. These are used for the delivery of mRNA-based vaccines, and in particular SM-102 forms part of the drug delivery system for the

Moderna COVID-19 vaccine The Moderna COVID19 vaccine (INN: elasomeran), sold under the brand name Spikevax, is a COVID-19 vaccine developed by American company Moderna, the United States National Institute of Allergy and Infectious Diseases (NIAID), and the Biomedi ...

. Lipid nanoparticles are an extension of earlier RNA transfection methods such as

cationic liposome Cationic liposomes are spherical structures that contain positively charged lipids. Cationic liposomes can vary in size between 40 nm and 500 nm, and they can either have one lipid bilayer (monolamellar) or multiple lipid bilayers (multila ...

s. Such systems are needed to protect the delicate mRNA molecules and shuttle them into cells without the immune system destroying them first. The nanoparticles enter the cells by triggering

receptor-mediated endocytosis Receptor-mediated endocytosis (RME), also called clathrin-mediated endocytosis, is a process by which cells absorb metabolites, hormones, proteins – and in some cases viruses – by the inward budding of the plasma membrane ( invagination). Th ...

. Ionisable lipids like SM-102 hold a neutral charge at

physiological pH Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical and ...

but are positively charged within the nanoparticle (the

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...

group is

protonated In chemistry, protonation (or hydronation) is the adding of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming a conjugate acid. (The complementary process, when a proton is removed from a Brønsted–Lowry acid ...

to form an

ammonium The ammonium cation is a positively-charged polyatomic ion with the chemical formula or . It is formed by the protonation of ammonia (). Ammonium is also a general name for positively charged or protonated substituted amines and quaternar ...

cation). This allows them to bind to the negatively charged backbone of mRNA. The rest of the nanoparticle is formed from

PEGylated PEGylation (or pegylation) is the process of both covalent and non-covalent attachment or amalgamation of polyethylene glycol (PEG, in pharmacy called macrogol) polymer chains to molecules and macrostructures, such as a drug, therapeutic protein ...

lipids, which help stabilize the particle, and

phospholipids Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typi ...

and

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell membr ...

molecules that contribute to the particle’s structure. SM-102 is also used for non-invasive

bioluminescence imaging Bioluminescence imaging (BLI) is a technology developed over the past decade that allows for the noninvasive study of ongoing biological processes. Recently, bioluminescence tomography (BLT) has become possible and several systems have become c ...

when SM-102 containing

luciferase Luciferase is a generic term for the class of oxidative enzymes that produce bioluminescence, and is usually distinguished from a photoprotein. The name was first used by Raphaël Dubois who invented the words '' luciferin'' and ''luciferase'' ...

-encoding mRNA is used for in-vivo luciferase expression in animal models.

Synthesis

The preparation of SM-102 was first described in a patent application to lipid nanoparticles by

Moderna Moderna, Inc. ( ) is an American pharmaceutical and biotechnology company based in Cambridge, Massachusetts that focuses on RNA therapeutics, primarily mRNA vaccines. These vaccines use a copy of a molecule called messenger RNA (mRNA) to pro ...

in 2017. The final step is an

alkylation Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...

reaction in which a

secondary amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...

is combined with a lipid bromo

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...

. :HO(CH₂)₂NH(CH₂)₇CO₂CH(C₈H₁₇)₂ + Br(CH₂)₅CO₂C₁₁H₂₃ → SM-102

References

Tertiary amines Lipids Ethanolamines Esters {{Amine-stub

Synthesis

See also

References