SM-102

SM-102
Names
	Preferred IUPAC name 9-Heptadecanyl 8-{(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino}octanoate
	Other names 1-Octylnonyl 8-[(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino]octanoate
Identifiers
CAS Number	2089251-47-6;
3D model (JSmol)	Interactive image;
ChemSpider	109107894 ;
PubChem CID	126697616;
UNII	T7OBQ65G2I;
CompTox Dashboard (EPA)	DTXSID301336730 ;
	InChI InChI=1S/C44H87NO5/c1-4-7-10-13-16-17-18-24-32-41-49-43(47)35-29-25-31-38-45(39-40-46)37-30-23-19-22-28-36-44(48)50-42(33-26-20-14-11-8-5-2)34-27-21-15-12-9-6-3/h42,46H,4-41H2,1-3H3 Key: BGNVBNJYBVCBJH-UHFFFAOYSA-N ;
	SMILES CCCCCCCCCCCOC(=O)CCCCCN(CCCCCCCC(=O)OC(CCCCCCCC)CCCCCCCC)CCO;
Properties
Chemical formula	C44H87NO5
Molar mass	710.182 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

SM-102 is a synthetic amino lipid which is used in combination with other lipids to form lipid nanoparticles.^[1] These are used for the delivery of mRNA-based vaccines,^[2]^[3]^[4] and in particular SM-102 forms part of the drug delivery system for the Moderna COVID-19 vaccine.^[5]^[6]^[7]

Lipid nanoparticles are an extension of earlier RNA transfection methods such as cationic liposomes.^[8] 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.

Ionisable lipids like SM-102 hold a relatively (/ close to) neutral charge at physiological pH but are positively charged within the nanoparticle (the amine group is protonated to form an ammonium cation). This allows them to bind to the negatively charged backbone of mRNA. The rest of the nanoparticle is formed from PEGylated lipids, which help stabilize the particle, and phospholipids and cholesterol molecules that contribute to the particle’s structure.^[8]

SM-102 is also used for non-invasive bioluminescence imaging when SM-102 containing luciferase-encoding mRNA is used for in-vivo luciferase expression in animal models.^[9]^[10]^[11]

Synthesis

The preparation of SM-102 was first described in a patent application to lipid nanoparticles by Moderna in 2017.^[12]^{: 139–142} The final step is an alkylation reaction in which a secondary amine is combined with a lipid bromo ester.

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

References

^ Hassett KJ, Benenato KE, Jacquinet E, Lee A, Woods A, Yuzhakov O, Himansu S, Deterling J, Geilich BM, Ketova T, Mihai C, Lynn A, McFadyen I, Moore MJ, Senn JJ, Stanton MG, Almarsson Ö, Ciaramella G, Brito LA (April 2019). "Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines". Molecular Therapy: Nucleic Acids. 15: 1–11. doi:10.1016/j.omtn.2019.01.013. PMC 6383180. PMID 30785039.
^ Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis of SARS-CoV-2 Infection (COVID-19), clinicaltrials.gov (US NIH/NLM), identifier NCT04283461. Accessed Jan. 17, 2021.
^ Clinical study protocol mRNA-1273-P301 Archived 2021-05-22 at the Wayback Machine, Amendment 6, ModernaTX, Inc., Dec. 23, 2020; accessed on line Jan. 17, 2021.
^ COVID-19 Vaccines: Update on Allergic Reactions, Contraindications, and Precautions, Clinician Outreach and Communication Activity (COCA) Webinar, Wednesday, December 30, 2020, CDC (US HHS); accessed on line Jan. 17, 2021.
^ Fact Sheet for Healthcare Providers Administering Vaccine (PDF). U.S. Food and Drug Administration (FDA) (Report). Moderna.
^ "Moderna COVID-19 Vaccine Standing Orders for Administering Vaccine to Persons 18 Years of Age and Older" (PDF). U.S. Centers for Disease Control and Prevention (CDC).
^ "Messengers of hope". editorial. Nat Biotechnol. 39 (1): 1. January 2021. doi:10.1038/s41587-020-00807-1. PMC 7771724. PMID 33376248.
^ ^a ^b Cross R. "Without these lipid shells, there would be no mRNA vaccines for COVID-19". Chemical & Engineering News. Retrieved 30 June 2021.
^ Buschmann MD, Carrasco MJ, Alishetty S, Paige M, Alameh MG, Weissman D (19 January 2021). "Nanomaterial Delivery Systems for mRNA Vaccines". Vaccines. 9 (1): 11. doi:10.3390/vaccines9010065. PMC 7836001. PMID 33478109.
^ Tao W, Davide JP, Cai M, Zhang GJ, South VJ, Matter A, Ng B, Zhang Y, Sepp-Lorenzino L (September 2010). "Noninvasive Imaging of Lipid Nanoparticle–Mediated Systemic Delivery of Small-Interfering RNA to the Liver". Molecular Therapy. 18 (9): 1657–1666. doi:10.1038/mt.2010.147. PMC 2956923. PMID 20628357. Retrieved 21 October 2021.
^ "SM-102 (CAS 2089251-47-6)". www.caymanchem.com. Retrieved 21 October 2021.
^ WO application 2017049245, Benenato K.E.; Kumarasinghe E.S. & Cornebise M., "Compounds and compositions for intracellular delivery of therapeutic agents", published 2017-03-23, assigned to ModernaTX, Inc.

[1] Hassett KJ, Benenato KE, Jacquinet E, Lee A, Woods A, Yuzhakov O, Himansu S, Deterling J, Geilich BM, Ketova T, Mihai C, Lynn A, McFadyen I, Moore MJ, Senn JJ, Stanton MG, Almarsson Ö, Ciaramella G, Brito LA (April 2019). "Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines". Molecular Therapy: Nucleic Acids. 15: 1–11. doi:10.1016/j.omtn.2019.01.013. PMC 6383180. PMID 30785039.

[2] Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis of SARS-CoV-2 Infection (COVID-19), clinicaltrials.gov (US NIH/NLM), identifier NCT04283461. Accessed Jan. 17, 2021.

[3] Clinical study protocol mRNA-1273-P301 Archived 2021-05-22 at the Wayback Machine, Amendment 6, ModernaTX, Inc., Dec. 23, 2020; accessed on line Jan. 17, 2021.

[4] COVID-19 Vaccines: Update on Allergic Reactions, Contraindications, and Precautions, Clinician Outreach and Communication Activity (COCA) Webinar, Wednesday, December 30, 2020, CDC (US HHS); accessed on line Jan. 17, 2021.

[5] Fact Sheet for Healthcare Providers Administering Vaccine (PDF). U.S. Food and Drug Administration (FDA) (Report). Moderna.

[CDC_standing_order-6] "Moderna COVID-19 Vaccine Standing Orders for Administering Vaccine to Persons 18 Years of Age and Older" (PDF). U.S. Centers for Disease Control and Prevention (CDC).

[7] "Messengers of hope". editorial. Nat Biotechnol. 39 (1): 1. January 2021. doi:10.1038/s41587-020-00807-1. PMC 7771724. PMID 33376248.

[C&E-8] Cross R. "Without these lipid shells, there would be no mRNA vaccines for COVID-19". Chemical & Engineering News. Retrieved 30 June 2021.

[9] Buschmann MD, Carrasco MJ, Alishetty S, Paige M, Alameh MG, Weissman D (19 January 2021). "Nanomaterial Delivery Systems for mRNA Vaccines". Vaccines. 9 (1): 11. doi:10.3390/vaccines9010065. PMC 7836001. PMID 33478109.

[10] Tao W, Davide JP, Cai M, Zhang GJ, South VJ, Matter A, Ng B, Zhang Y, Sepp-Lorenzino L (September 2010). "Noninvasive Imaging of Lipid Nanoparticle–Mediated Systemic Delivery of Small-Interfering RNA to the Liver". Molecular Therapy. 18 (9): 1657–1666. doi:10.1038/mt.2010.147. PMC 2956923. PMID 20628357. Retrieved 21 October 2021.

[11] "SM-102 (CAS 2089251-47-6)". www.caymanchem.com. Retrieved 21 October 2021.

[WO2017-12] WO application 2017049245, Benenato K.E.; Kumarasinghe E.S. & Cornebise M., "Compounds and compositions for intracellular delivery of therapeutic agents", published 2017-03-23, assigned to ModernaTX, Inc.

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Synthesis

See also

References