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Ionisable lipids like SM-102 hold a 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.<ref name=C&E />
Ionisable lipids like SM-102 hold a 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.<ref name=C&E />

SM-102 is also used for non-invasive [[bioluminescence imaging]] when lipid nanoparticles like SM-102 containing [[luciferase]]-encoding mRNA are used for in-vivo luciferase expression in animal models.<ref>{{cite journal |last1=Buschmann |first1=Michael D. |last2=Carrasco |first2=Manuel J. |last3=Alishetty |first3=Suman |last4=Paige |first4=Mikell |last5=Alameh |first5=Mohamad Gabriel |last6=Weissman |first6=Drew |title=Nanomaterial Delivery Systems for mRNA Vaccines |journal=Vaccines |date=19 January 2021 |volume=9 |issue=1 |page=11 |pages=65 |doi=10.3390/vaccines9010065 |url=https://doi.org/10.3390/vaccines9010065 |access-date=21 October 2021 |language=en}}</ref><ref>{{cite journal |last1=Tao |first1=Weikang |last2=Davide |first2=Joseph P |last3=Cai |first3=Mingmei |last4=Zhang |first4=Guo-Jun |last5=South |first5=Victoria J |last6=Matter |first6=Andrea |last7=Ng |first7=Bruce |last8=Zhang |first8=Ye |last9=Sepp-Lorenzino |first9=Laura |title=Noninvasive Imaging of Lipid Nanoparticle–Mediated Systemic Delivery of Small-Interfering RNA to the Liver |journal=Molecular Therapy |date=September 2010 |volume=18 |issue=9 |page=1 |pages=1657–1666 |doi=10.1038%2Fmt.2010.147 |url=https://dx.doi.org/10.1038%2Fmt.2010.147 |access-date=21 October 2021}}</ref><ref>{{cite web |title=SM-102 (CAS 2089251-47-6) |url=https://www.caymanchem.com/product/33474/sm-102#reference61317 |website=www.caymanchem.com |access-date=21 October 2021 |language=en}}</ref>
==Synthesis==
==Synthesis==
The preparation of SM-102 was first described in a patent application to lipid nanoparticles by [[Moderna]] in 2017.<ref name=WO2017>{{cite patent |country=WO |number=2017049245 |status=application |pubdate=2017-03-23 |fdate=2016-09-16 |pridate=2015-09-17 |invent1 =Benenato K.E. |invent2=Kumarasinghe E.S. |invent3=Cornebise M. |title=Compounds and compositions for intracellular delivery of therapeutic agents |assign1=ModernaTX, Inc.}}</ref>{{rp|139–142}} The final step is an [[alkylation]] reaction in which a [[Amine|secondary amine]] is combined with a lipid bromo [[ester]].
The preparation of SM-102 was first described in a patent application to lipid nanoparticles by [[Moderna]] in 2017.<ref name=WO2017>{{cite patent |country=WO |number=2017049245 |status=application |pubdate=2017-03-23 |fdate=2016-09-16 |pridate=2015-09-17 |invent1 =Benenato K.E. |invent2=Kumarasinghe E.S. |invent3=Cornebise M. |title=Compounds and compositions for intracellular delivery of therapeutic agents |assign1=ModernaTX, Inc.}}</ref>{{rp|139–142}} The final step is an [[alkylation]] reaction in which a [[Amine|secondary amine]] is combined with a lipid bromo [[ester]].

Revision as of 07:14, 21 October 2021

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
3D model (JSmol)
ChemSpider
UNII
  • 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 checkY
    Key: BGNVBNJYBVCBJH-UHFFFAOYSA-N checkY
  • CCCCCCCCCCCOC(=O)CCCCCN(CCCCCCCC(=O)OC(CCCCCCCC)CCCCCCCC)CCO
Properties
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).

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 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 lipid nanoparticles like SM-102 containing luciferase-encoding mRNA are 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

See Also

Moderna COVID-19 vaccine nanoparticle ingredients

References

  1. ^ Hassett, Kimberly J.; Benenato, Kerry E.; Jacquinet, Eric; Lee, Aisha; Woods, Angela; Yuzhakov, Olga; Himansu, Sunny; Deterling, Jessica; Geilich, Benjamin M.; Ketova, Tatiana; Mihai, Cosmin; Lynn, Andy; McFadyen, Iain; Moore, Melissa J.; Senn, Joseph J.; Stanton, Matthew G.; Almarsson, Örn; Ciaramella, Giuseppe; Brito, Luis A. (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, 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.
  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.
  8. ^ a b Cross, Ryan. "Without these lipid shells, there would be no mRNA vaccines for COVID-19". Chemical & Engineering News. Retrieved 30 June 2021.
  9. ^ Buschmann, Michael D.; Carrasco, Manuel J.; Alishetty, Suman; Paige, Mikell; Alameh, Mohamad Gabriel; Weissman, Drew (19 January 2021). "Nanomaterial Delivery Systems for mRNA Vaccines". Vaccines. 9 (1): 11. doi:10.3390/vaccines9010065. Retrieved 21 October 2021. {{cite journal}}: More than one of |pages= and |page= specified (help)CS1 maint: unflagged free DOI (link)
  10. ^ Tao, Weikang; Davide, Joseph P; Cai, Mingmei; Zhang, Guo-Jun; South, Victoria J; Matter, Andrea; Ng, Bruce; Zhang, Ye; Sepp-Lorenzino, Laura (September 2010). "Noninvasive Imaging of Lipid Nanoparticle–Mediated Systemic Delivery of Small-Interfering RNA to the Liver". Molecular Therapy. 18 (9): 1. doi:10.1038%2Fmt.2010.147. Retrieved 21 October 2021. {{cite journal}}: Check |doi= value (help); More than one of |pages= and |page= specified (help)
  11. ^ "SM-102 (CAS 2089251-47-6)". www.caymanchem.com. Retrieved 21 October 2021.
  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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