This document provides an overview of mRNA-based therapeutics, detailing the definition, action mechanism, and key advances in the field since 1961. It highlights the structure of mRNA, its therapeutic applications in various diseases, and the strategies for effective mRNA delivery and optimization. Additionally, Creative Biolabs offers services related to mRNA synthesis and development for various therapeutic applications.

1. mRNA-based
Therapeutics
Overview of a class of drugs
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2. mRNA Definition
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CONTENTS
01
Timeline of mRNA Therapeutics
02
Action Mechanism
03
Design and Optimization for mRNA Drug
04
Therapeutic mRNA Applications
05
Creative Biolabs’ Services
06
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3. mRNA Definition
Definition
mRNA is a single stranded ribonucleic acid transcribed from DNA and carries genetic
information.
mRNA is the middleman of central dogma of molecular biology, which is responsible for
transmitting genetic information and directly guiding protein synthesis.
Structure
The structure of mRNA can be divided into five parts: 5' end cap, 5' non-transcriptional region
(UTR), open reading frame encoding antigen, 3' UTR, and polyadenine tail.
Understanding the structure and function of mRNA and its metabolism in eukaryotic cells is an
important basis for the development of mRNA-based therapy.
Overview of
a class of drugs
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5’ Cap
5’ UTR 3’ UTR
ORF
AAAA

4. Timeline of key advances in mRNA therapeutics
1961 1989 1990 2001
1999
1995 2009 2010 2013 2015 2017 2020
• Discovery of
mRNA
• Demonstration that
naked mRNA injected into
mice was translated
• First report of an anti-
tumour T cell response
after mRNA injection in vivo
• First human cancer
immunotherapy by
direct mRNA injection
• Protein replacement
with LNPs carrying
factor IX mRNA
restores normal
protein levels in a
haemophilia B animal
model
• Electroporation of
CRISPR RNAs into
mouse zygotes for
gene editing
• Development of
cationic lipid-
mediated mRNA
delivery
• Lipofectin
commercialized
• First cancer immunotherapy
study using mRNA encoding
cancer antigens
• First clinical trial using
DCs ex vivo transfected
with mRNA
• iPSC
generation
with mRNA
• First in-human test
of personalized
mRNA cancer
vaccine
• Clinical trial of LNP-
mRNA formulations as
influenza vaccines
• Clinical trial of LNP-
mRNA formulations for
protein replacement
therapies
• mRNA-1273 and
BNT162b (LNP-
mRNA
formulations)
COVID-19 mRNA
vaccines
obtained
authorization
from regulatory
agencies in
multiple
countries
Timeline of mRNA Therapeutics
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5. • mRNA drugs are synthesized by in vitro transcription
of DNA templates, such as linearized plasmids or PCR
products.
• The main action environment of mRNA drugs is
in the cytoplasm.
• Once the encoded protein has been generated,
its destination is determined by signal
peptides.
• The protein product encoded by mRNA is
degraded by proteasome and presented to T
cells by MHC to produce immune response.
Sahin, U., Karikó, K. & Türeci, Ö. mRNA-based therapeutics — developing a new class of drugs. Nat Rev Drug Discov 13, 759–780 (2014).
Action Mechanism
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6. Unmodified mRNA has innate immunogenicity, and using modified nucleotides to produce mRNA can reduce immunogenicity.
Design and Optimization for mRNA Drug
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5’ UTR 3’ UTR
ORF
AAAA
The 5’-cap region plays an important role
in effective translation and mRNA
degradation, so adding a special hat
structure can reduce the synthetic error
rate and improve the translation efficiency. The coding region determines the specificity of
antigens. By optimizing the use of codons and
bases, the translation efficiency of mRNA
templates can be improved and the attack of
endonuclease can be reduced.
The non-coding region can regulate the transport
and translation efficiency of mRNA, and
optimizing the non-coding region can improve the
stability and translation level of mRNA.
The Poly (A) tail determines the stability of
mRNA. By adding modified nucleotides to the
tail, mRNA deadenylation can be avoided and
translation can be carried out normally.
5’ Cap
Poly (A) tail

7. Delivery System
Lipids Lipid Nanoparticle Lipid-polymer Hybrid Nanoparticle
Nanoparticle encapsulation physically protects
mRNA from degradation and, depending on the
specific chemistry, can aid in cellular uptake and
endosomal escape.
The wide application of therapeutic mRNA requires efficient and safe delivery. A desired mRNA delivery vehicle must have the following properties:
1) Protection of mRNA from extra-cellular nuclease digestion; 2) Cell-specific uptake;
3) Endosomal escape; 4) The desired level of delivery vehicle specific immunostimulatory properties;
5) Efficient clearance of delivery vehicle components; 6) Low toxicity.
At present, commonly used delivery systems include lipoplex, lipid nanoparticle, and lipid-polymer hybrid nanoparticle.
Lipid Bilayer Lipid Monolayer
mRNA Drug Development Strategy
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The hybrid delivery system has shown promising results for the
delivery of mRNA, with the mRNA encapsulated in a hybrid
nanoparticle composed of the lipid-like material with a polymeric
PLGA core.
Lipids and lipid-like materials represent
the second major class of nanoparticle-
based delivery vehicles for RNA.

8. Therapeutic mRNA Applications
Field of Application Examples
Cancer
Immunotherapies
Melanoma, prostate cancer, haematological
malignancies, ovarian cancer, lymphoma, leukaemia,
mesothelioma, renal cell carcinoma, pancreatic cancer,
metastatic malignancies, colon cancer, etc
Infectious Disease
Vaccines
Influenza, tuberculosis, respiratory tract infection, tick-
borne encephalitis, HIV, etc.
Allergy Tolerization
Allergies for peanut, egg white, grass pollen, and dust
mite
Protein-replacement and
Supplementation
Therapies
Diabetes insipidus, anaemia, congenital lung disease,
asthma, myocardial infarction, melanoma, Autoimmune
diabetes, Autoimmune myocarditis,
Inflammation, etc.
Genome Engineering Genome engineering
Genetic Reprogramming Generating iPSCs, and disease models
Overview of
a class of drugs
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9. Part of mRNA Drug Research Pipeline
Drug R&D Enterprise Type Indication
BNT162 Biontech Vaccine COVID-19
MRT5005 Translate Bio Drug Cystic Fibrosis
mRNA 1273 Moderna Vaccine COVID-19
LUNAR-OTC Arcturus Drug OTC Deficiency
A004 etheRNA Drug Not clear
PAN004 Pantherna Therapeutics Drug ARDS
HGC019 Gennova Vaccine COVID-19
ETH42 ethris Drug PCD
TB Vaccine Stemi RNA Vaccine Tuberculosis
EXG34217 elixirger Drug
Telomere Shortening
Bone Marrow Failure Disease
mCura1 Mercurna Drug CKD
RV1730 RNA immune Vaccine COVID-19
Therapeutic mRNA Applications
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10. mRNA Synthesis
Delivery Vehicle for mRNA
mRNA Modification
mRNA-based Cell Reprogramming
mRNA Stability Test Service
One-stop mRNA Therapeutics Development
mRNA-based Assays
Custom Service
Creative Biolabs’ Services
Overview of a class of drugs
*Chemical Synthesis of mRNA
* IVT Synthesis of mRNA
*Lipid-based Vectors
*Polymer-based Vectors
*Hybrid Vectors
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11. mRNA-based
Therapeutics
Overview of a class of drugs
Address: SUITE 203, 17 Ramsey Road, Shirley, NY 11967, USA
Email: info@creative-biolabs.com
Web: www.creative-biolabs.com
CREATIVE
BIOLABS