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Lipid Nanoparticle-based
mRNA Vaccine
Tel: 1-631-357-2254
Email: info@creative-biolabs.com
SUITE 203, 17 Ramsey Road, Shirley, NY 11967, USA
Content
Timeline of mRNA and LNP Development
The Nobel Prize in Physiology or Medicine 2023
COVID-19 Vaccine Involves Liposomes and mRNA
Key Features of BNT162b2 and mRNA-1273 Vaccines
Advantages of Using Liposomes to Deliver mRNA
Mechanism of LNP-based mRNA Vaccine
LNP-based mRNA Vaccines and Therapeutics
The Process of LNPs-based mRNA Vaccine Development
Creative Biolabs’ Services and Products
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(Xucheng H, et al., 2021)
Timeline of mRNA and LNP Development
1961
Discovery of mRNA
and its function
1978
Development of liposome
mRNA formulations
1993
Development of liposome-mRNA
formulations as influenza vaccine
2020
· mRNA-1273 and BNT162b (LNP-mRNA
formulations) COVID-19 mRNA vaccines
obtained authorization from
regulatory agencies in multiple countries
· Clinical trial of LNP formulations delivering
gene-editing components for genetic disorders
(NCTO4601051)
1965
Development of
liposomes
1989
Development of cationic
LNP-mRNA formulations
2017
· Clinical trial of LNP-mRNA formulations
as influenza vaccines (NCT03076385)
· Clinical trial of LNP-mRNA formulations
for protein replacement therapies
(NCT03375047)
2023
2023 Nobel Prize in
Physiology or Medicine-
development of effective
mRNA vaccines against
COVID-19
3
In 2023, two pioneers in the field of RNA biology, Katalin Karikó and Drew
Weissman, received the esteemed Nobel Prize for Physiology or Medicine.
Their pivotal discoveries concerning nucleoside base modifications have
revolutionized medicinal biology, notably spearheading the development of
mRNA vaccines that effectively combat COVID-19.
Karikó and Weissman's breakthrough elucidated how to strategically modify
nucleosides, the fundamental building blocks of RNA, thereby preventing the
body’s immune system from indiscriminately attacking introduced mRNA.
A crucial aspect of their work is the role of lipid nanoparticles, specifically
liposomes. Liposomes act as effective carriers that encapsulate and deliver
the modified vaccines safely to our cells. This method sidesteps the immune
evasion issue faced by mRNA and constitutes a significant development in the
localization and precision of vaccine delivery.
The Nobel Prize in Physiology or
Medicine 2023
4
The journey of integrating liposomes into mRNA vaccines is a remarkable feat in medical science.
The urgency for efficient vaccine delivery systems was acutely felt during the COVID-19
pandemic. Traditional approaches proved inadequate, primarily due to the vulnerability of mRNA
molecules, which were too fragile to survive in the human body long enough to provoke a
substantial immune response. However, a breakthrough was achieved by leveraging the unique
properties of liposomes.
Discovered by biophysicist Alec Bangham in the 1960s, liposomes transitioned from simple cell
membrane models to sophisticated drug delivery systems. Their biocompatibility and ability to
encapsulate both water- and lipid-soluble materials made them ideal candidates for medical
applications. Liposomes were soon adopted for delivering drugs to targeted body areas.
Significant progress was made when liposomes were recognized as potent immunological
adjuvants. They could elicit a stronger antibody response compared to traditional methods. This
potential was harnessed in the development of mRNA vaccines, where liposomes served not
only as protective carriers for the fragile mRNA but also as enhancers of the immune response.
By stabilizing mRNA within the bloodstream and facilitating its entry into the cells, liposomes
became an integral component of the BNT162b2 and mRNA-1273 vaccines.
COVID-19 Vaccine Involves Liposomes and mRNA
5
Key Features of BNT162b2 and mRNA-1273 Vaccines
Key Features BNT162b2 mRNA-1273
mRNA
modRNA encoding the viral spike
glycoprotein of SARS-CoV-2
Synthetic mRNA encoding the spike glycoprotein of
SARS-CoV-2
Carrier Platform Lipid nanoparticles Lipid nanoparticles
Lipids
ALC-0315
ALC-0159
DSPC
Cholesterol
SM-102
PEG2000-DMG,
1,2-distearoyl-sn-glycero-3-phosphocholine
Cholesterol
EUA Approval by FDA 11th December 2020 18th December 2020
Dose 0.3 ml containing 30 µg vaccine 0.5 ml containing 100 µg vaccine
Efficacy 95% against the SARS-CoV infection 94.1% against the SARS-CoV infection
Stability/Storage -60 to -80 °C (6 months), 2-8 °C (5 days) -15 to -25 °C (6 months), 2-8 °C (30 days)
(Wilson B, et al., 2022)
6
(Riaz, 2018)
 Liposomes are biodegradable, easy to prepare and can
entrap mRNA quantitatively
 Liposome-entrapped mRNA fully protected from nuclease
attack in the blood circulation
 Liposomal mRNA enters the cytoplasm of cells by
endocytosis
 Cationic liposomal mRNA escapes the lysosomotropic
pathway to end up intact in the cytoplasm
 Within the cytoplasm, mRNA is expressed as the spike
protein whereupon, by an as yet unclear mechanism,
liposomes or their remnants exert their immunological
adjuvant action
Advantages of Using Liposomes
to Deliver mRNA
7
Mechanism of LNP-based mRNA Vaccine
8
mRNA vaccines have revolutionized vaccine development because of their
high efficacies, accelerated development cycles, and potential for low-cost
manufacture. The rapid development of mRNA vaccines would not have
been possible without advances in LNP technologies to deliver nucleic acids.
LNP-based mRNA vaccines have entered clinical trials for multiple infectious
diseases, such as vaccines against the Zika virus, cytomegalovirus,
tuberculosis, and modified nucleoside mRNA influenza.
mRNA therapeutic vaccines also have vast potential in cancer
immunotherapy against melanoma, ovarian cancer, breast cancer, and other
solid tumors.
LNP-based mRNA Vaccines and
Therapeutics
补充合适配图
9
The Process of LNPs-based mRNA Vaccine Development
mRNA Design and
Synthesis
LNP Formulation In Vitro Testing Preclinical Studies
Encapsulating mRNA
in LNPs
These LNPs are structured
to encapsulate and protect
the mRNA , ensuring its
delivery into cells.
Lipid Synthesis
Synthesizing the special
lipids that make up the
LNPs
Size and Stability
OptimizationmRNA in LNPs
The LNPs are adjusted for size
and stability to ensure efficient
absorption in the human body
and optimize distribution in the
body and intracellular release.
Surface Modification
The LNPs are surface-modified,
such as adding targeting ligands
or polyethylene glycol (PEG)
modifications, to improve
stability and biocompatibility.
10
Services
Creative Biolabs’ Services and Products
• Custom Lipid Synthesis
• Liposome Encapsulated Nucleic Acid Development
• LNP Delivery System Development
• Lipid-based Functionalized Delivery System Development
• Formulation Analysis and Characterization
 Structure and Composition Analysis
 Basic Characterization
 In Vitro Release Kinetics Analysis
 Formulation Stability Evaluation
 Formulation Safety Evaluation
• Pharmacodynamic Study
 PK-PD Analysis
 Multi-omics Analysis
Creative Biolabs provides one-stop customized services and products to aid your LNPs-
based mRNA vaccine development.
Products
• Liposomes
 Plain Liposome
 Cationic Liposome
 Clodronate Liposome
 Fluorescent Liposome
 Drug-loaded Liposome
 Immunoliposomes
 Liposomal Vaccine or Adjuvant
• Phospholipids
 PA & LPA
 PC & LPC
 PE & LPE
 PG & LPG
 PI & LPI
 PS & LPS
 Cardiolipin
 Ether Lipids
• Lipids
 PEGylated Lipids
 Lipids for LNP
11
Tel: 1-631-357-2254 info@creative-biolabs.com
SUITE 203, 17 Ramsey Road, Shirley, NY 11967, USA
Contact With
Our Company

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Lipid Nanoparticle-based mRNA Vaccine Creative Biolabs.pptx

  • 1. Lipid Nanoparticle-based mRNA Vaccine Tel: 1-631-357-2254 Email: info@creative-biolabs.com SUITE 203, 17 Ramsey Road, Shirley, NY 11967, USA
  • 2. Content Timeline of mRNA and LNP Development The Nobel Prize in Physiology or Medicine 2023 COVID-19 Vaccine Involves Liposomes and mRNA Key Features of BNT162b2 and mRNA-1273 Vaccines Advantages of Using Liposomes to Deliver mRNA Mechanism of LNP-based mRNA Vaccine LNP-based mRNA Vaccines and Therapeutics The Process of LNPs-based mRNA Vaccine Development Creative Biolabs’ Services and Products 2 3 4 5 6 7 8 9 10 11
  • 3. (Xucheng H, et al., 2021) Timeline of mRNA and LNP Development 1961 Discovery of mRNA and its function 1978 Development of liposome mRNA formulations 1993 Development of liposome-mRNA formulations as influenza vaccine 2020 · mRNA-1273 and BNT162b (LNP-mRNA formulations) COVID-19 mRNA vaccines obtained authorization from regulatory agencies in multiple countries · Clinical trial of LNP formulations delivering gene-editing components for genetic disorders (NCTO4601051) 1965 Development of liposomes 1989 Development of cationic LNP-mRNA formulations 2017 · Clinical trial of LNP-mRNA formulations as influenza vaccines (NCT03076385) · Clinical trial of LNP-mRNA formulations for protein replacement therapies (NCT03375047) 2023 2023 Nobel Prize in Physiology or Medicine- development of effective mRNA vaccines against COVID-19 3
  • 4. In 2023, two pioneers in the field of RNA biology, Katalin Karikó and Drew Weissman, received the esteemed Nobel Prize for Physiology or Medicine. Their pivotal discoveries concerning nucleoside base modifications have revolutionized medicinal biology, notably spearheading the development of mRNA vaccines that effectively combat COVID-19. Karikó and Weissman's breakthrough elucidated how to strategically modify nucleosides, the fundamental building blocks of RNA, thereby preventing the body’s immune system from indiscriminately attacking introduced mRNA. A crucial aspect of their work is the role of lipid nanoparticles, specifically liposomes. Liposomes act as effective carriers that encapsulate and deliver the modified vaccines safely to our cells. This method sidesteps the immune evasion issue faced by mRNA and constitutes a significant development in the localization and precision of vaccine delivery. The Nobel Prize in Physiology or Medicine 2023 4
  • 5. The journey of integrating liposomes into mRNA vaccines is a remarkable feat in medical science. The urgency for efficient vaccine delivery systems was acutely felt during the COVID-19 pandemic. Traditional approaches proved inadequate, primarily due to the vulnerability of mRNA molecules, which were too fragile to survive in the human body long enough to provoke a substantial immune response. However, a breakthrough was achieved by leveraging the unique properties of liposomes. Discovered by biophysicist Alec Bangham in the 1960s, liposomes transitioned from simple cell membrane models to sophisticated drug delivery systems. Their biocompatibility and ability to encapsulate both water- and lipid-soluble materials made them ideal candidates for medical applications. Liposomes were soon adopted for delivering drugs to targeted body areas. Significant progress was made when liposomes were recognized as potent immunological adjuvants. They could elicit a stronger antibody response compared to traditional methods. This potential was harnessed in the development of mRNA vaccines, where liposomes served not only as protective carriers for the fragile mRNA but also as enhancers of the immune response. By stabilizing mRNA within the bloodstream and facilitating its entry into the cells, liposomes became an integral component of the BNT162b2 and mRNA-1273 vaccines. COVID-19 Vaccine Involves Liposomes and mRNA 5
  • 6. Key Features of BNT162b2 and mRNA-1273 Vaccines Key Features BNT162b2 mRNA-1273 mRNA modRNA encoding the viral spike glycoprotein of SARS-CoV-2 Synthetic mRNA encoding the spike glycoprotein of SARS-CoV-2 Carrier Platform Lipid nanoparticles Lipid nanoparticles Lipids ALC-0315 ALC-0159 DSPC Cholesterol SM-102 PEG2000-DMG, 1,2-distearoyl-sn-glycero-3-phosphocholine Cholesterol EUA Approval by FDA 11th December 2020 18th December 2020 Dose 0.3 ml containing 30 µg vaccine 0.5 ml containing 100 µg vaccine Efficacy 95% against the SARS-CoV infection 94.1% against the SARS-CoV infection Stability/Storage -60 to -80 °C (6 months), 2-8 °C (5 days) -15 to -25 °C (6 months), 2-8 °C (30 days) (Wilson B, et al., 2022) 6
  • 7. (Riaz, 2018)  Liposomes are biodegradable, easy to prepare and can entrap mRNA quantitatively  Liposome-entrapped mRNA fully protected from nuclease attack in the blood circulation  Liposomal mRNA enters the cytoplasm of cells by endocytosis  Cationic liposomal mRNA escapes the lysosomotropic pathway to end up intact in the cytoplasm  Within the cytoplasm, mRNA is expressed as the spike protein whereupon, by an as yet unclear mechanism, liposomes or their remnants exert their immunological adjuvant action Advantages of Using Liposomes to Deliver mRNA 7
  • 8. Mechanism of LNP-based mRNA Vaccine 8
  • 9. mRNA vaccines have revolutionized vaccine development because of their high efficacies, accelerated development cycles, and potential for low-cost manufacture. The rapid development of mRNA vaccines would not have been possible without advances in LNP technologies to deliver nucleic acids. LNP-based mRNA vaccines have entered clinical trials for multiple infectious diseases, such as vaccines against the Zika virus, cytomegalovirus, tuberculosis, and modified nucleoside mRNA influenza. mRNA therapeutic vaccines also have vast potential in cancer immunotherapy against melanoma, ovarian cancer, breast cancer, and other solid tumors. LNP-based mRNA Vaccines and Therapeutics 补充合适配图 9
  • 10. The Process of LNPs-based mRNA Vaccine Development mRNA Design and Synthesis LNP Formulation In Vitro Testing Preclinical Studies Encapsulating mRNA in LNPs These LNPs are structured to encapsulate and protect the mRNA , ensuring its delivery into cells. Lipid Synthesis Synthesizing the special lipids that make up the LNPs Size and Stability OptimizationmRNA in LNPs The LNPs are adjusted for size and stability to ensure efficient absorption in the human body and optimize distribution in the body and intracellular release. Surface Modification The LNPs are surface-modified, such as adding targeting ligands or polyethylene glycol (PEG) modifications, to improve stability and biocompatibility. 10
  • 11. Services Creative Biolabs’ Services and Products • Custom Lipid Synthesis • Liposome Encapsulated Nucleic Acid Development • LNP Delivery System Development • Lipid-based Functionalized Delivery System Development • Formulation Analysis and Characterization  Structure and Composition Analysis  Basic Characterization  In Vitro Release Kinetics Analysis  Formulation Stability Evaluation  Formulation Safety Evaluation • Pharmacodynamic Study  PK-PD Analysis  Multi-omics Analysis Creative Biolabs provides one-stop customized services and products to aid your LNPs- based mRNA vaccine development. Products • Liposomes  Plain Liposome  Cationic Liposome  Clodronate Liposome  Fluorescent Liposome  Drug-loaded Liposome  Immunoliposomes  Liposomal Vaccine or Adjuvant • Phospholipids  PA & LPA  PC & LPC  PE & LPE  PG & LPG  PI & LPI  PS & LPS  Cardiolipin  Ether Lipids • Lipids  PEGylated Lipids  Lipids for LNP 11
  • 12. Tel: 1-631-357-2254 info@creative-biolabs.com SUITE 203, 17 Ramsey Road, Shirley, NY 11967, USA Contact With Our Company