This slide provides a comprehensive overview of lipid nanoparticle-based mRNA Vaccine development, detailing the technological timeline, the 2023 Nobel Prize-winning science behind the vaccines, and the specifics of COVID-19 vaccine candidates BNT162b2 and mRNA-1273. It also explores the advantages of liposomes in mRNA delivery, the intricate mechanisms of LNP-based vaccines, their therapeutic potential beyond COVID-19, and the rigorous development process. Creative Biolabs supports these innovations with specialized services and products, pushing the boundaries of medical science.
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
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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
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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
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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
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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)
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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
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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
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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.
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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
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