Key highlights

• mRNA therapeutics offer fast, cell-free synthesis with enhanced scalability, precision, and safety, eliminating risks like genomic integration.
• mRNA provides a tailored approach to overcoming “undruggable” targets and off-target effects that can be seen with small molecule drugs and CRISPR gene editing.
• mRNA’s ability to harness the body’s natural protein production is reshaping healthcare across multiple therapeutic areas.

Introduction

In 2020, messenger RNA (mRNA) based therapeutics were thrown into the spotlight. The success of Moderna and Pfizer’s coronavirus vaccines demonstrated the rapid development, scalable production, and robust immune response that mRNA offers over conventional vaccines, which were either protein-based or relied on inactivated pathogens. This breakthrough has not only redefined how we approach vaccines but has also opened the door to a new class of mRNA-based therapeutics poised to revolutionize the entire landscape of medicine.

By harnessing the body’s own cellular machinery to produce proteins on demand, mRNA therapeutics offer unmatched versatility and safety. Unlike traditional methods that require complex manufacturing processes and face challenges such as stability issues or genomic integration, mRNA-based treatments provide a streamlined and efficient alternative. In this eBlog, we examine how mRNA is revolutionizing conventional therapies—from improving recombinant protein treatments to enabling cutting-edge gene editing.

Traditional versus mRNA-based therapeutics

Therapeutic Modality	Traditional Approach	mRNA Therapeutics
Recombinant Proteins	Complex cell-based production with extensive purification	In vivo production streamlines manufacturing
Gene Therapy	DNA vectors with integration risks and persistent expression	Transient cytoplasmic expression avoids integration risks
Cell Therapy	Permanent modification via viral vectors	Temporary reprogramming enhances safety
Small Molecule Drugs	Challenges with “undruggable” targets and off-target effects	Enables direct protein replacement for precision targeting
CRISPR Gene Editing	DNA-based delivery with risks of persistent expression and integration	Transient mRNA delivery minimizes off-target risks

The mRNA advantage

At its core, mRNA therapeutics work by delivering the genetic instructions needed for a patient’s cells to produce a desired protein. This approach comes with several key benefits:

• Rapid development and scalability: mRNA can be synthesized using cell-free processes, enabling rapid production and easier scalability compared to conventional cell-based methods.
• Precision and flexibility: With the ability to encode virtually any protein, mRNA platforms are adaptable to a wide range of diseases—from infectious diseases to complex genetic disorders.
• Enhanced safety: Because mRNA does not integrate into the genome, it significantly reduces risks associated with permanent genetic alterations.

Next, we dive deeper into mRNA’s transformative potential across multiple therapeutic areas.

1. Recombinant protein therapies

Traditional approach

Recombinant protein therapies have long been used to produce monoclonal antibodies, hormones, enzymes, and cytokines through cell-based systems (bacteria, yeast, or mammalian cells). However, these methods often encounter significant challenges:

• Complex manufacturing: Multi-step processes with rigorous quality control and extensive purification steps drive up costs and extend production timelines.
• Stability issues: Many proteins have short in vivo half-lives and require modifications, such as PEGylation, to remain effective.
• Limited intracellular targeting: Recombinant proteins typically function outside cells, which restricts their use against intracellular targets.

mRNA’s impact

mRNA therapeutics address these challenges by instructing the patient’s own cells to produce the protein, offering several advantages:

• In situ production: By synthesizing proteins directly within the patient, the need for complex downstream purification is bypassed.
• Accurate post-translational modifications: Endogenous protein production ensures proper human-specific modifications, which can improve function and reduce immunogenicity.
• Broader target range: mRNA enables production of proteins that act both extracellularly and intracellularly, expanding the range of treatable conditions.

2. Gene therapy

Traditional approach

Traditional gene therapy often uses DNA delivered via viral or non-viral vectors. Despite its promise, this method comes with inherent risks:

• Genomic integration: There is a risk that the introduced DNA may integrate into the host genome, potentially leading to insertional mutagenesis.
• Persistent expression: Continuous expression may lead to unintended effects if the therapeutic protein is needed only temporarily.

mRNA’s impact

Using mRNA for gene therapy provides a safer, transient alternative:

• Temporary expression: mRNA is naturally degraded over time, offering controlled protein production without permanent genomic alteration.
• Eliminated integration risks: Operating exclusively in the cytoplasm, mRNA avoids the risk of integrating into the genome.

3. Cell therapy

Traditional approach

Cell therapies, such as CAR-T cell treatments, generally involve ex vivo modification of cells using viral vectors, which can be both time-consuming and costly. Moreover, permanent genetic modifications raise long-term safety concerns.

mRNA’s impact

mRNA enables temporary reprogramming of cells, offering significant advantages:

• Transient reprogramming: Cells can be modified temporarily using mRNA, allowing for precise control over therapeutic effects without permanent genomic changes.
• Accelerated development: This approach speeds up the optimization and prototyping of cell therapies, especially in areas like oncology and regenerative medicine.

4. Small molecule drugs

Traditional approach

Small molecule drugs have been the backbone of many therapeutic interventions. However, they can struggle with:

• "Undruggable" targets: Certain intracellular proteins or protein–protein interactions are difficult to modulate using small molecules.
• Off-Target effects: Achieving the necessary specificity to avoid side effects can be challenging.

mRNA’s impact

mRNA opens new avenues where small molecules fall short:

• Protein replacement: Instead of attempting to modulate a challenging target, mRNA can instruct cells to produce the missing or dysfunctional protein.
• Precision therapy: By enabling the production of highly specific proteins, mRNA minimizes off-target effects and offers a tailored therapeutic approach.

5. CRISPR gene editing

Traditional approach

CRISPR gene editing has revolutionized our understanding of genetics. However, traditional delivery methods that use DNA to encode CRISPR components can lead to:

• Persistent expression: Prolonged expression of gene editing tools increases the risk of off-target effects.
• Genomic integration: DNA-based methods risk inadvertent integration of exogenous sequences into the genome.

mRNA’s impact

Delivering CRISPR components via mRNA provides a safer and more controlled alternative:

• Transient expression: mRNA ensures that gene editing tools, such as Cas9 and guide RNAs, are expressed only for a limited time, reducing off-target risks.
• Enhanced safety profile: With minimal risk of genomic integration, mRNA-based CRISPR delivery offers a more precise gene editing strategy.

You can learn more about how mRNA is applied to gene editing with our webinar on characterizing mRNA-based CRISPR therapies here.

Conclusion

mRNA therapeutics are not merely another class of drugs; they are fundamentally transforming the way we approach modern medicine. By harnessing the body’s natural protein production capabilities, mRNA offers rapid, scalable, and precise therapeutic solutions. Whether it’s supplanting traditional recombinant protein therapies, reshaping gene and cell therapies, or providing safer alternatives for small molecule drugs and CRISPR gene editing, mRNA is revolutionizing healthcare as we know it.

As mRNA technology continues to mature, its integration across multiple therapeutic areas promises to usher in a new era of precision medicine. Our eMERGE platform provides our partners with the necessary support to ensure successful mRNA drug development. Contact us today to learn more.

References

1. 1. Pardi et al.
2. 2. Sahin et al.
3. 3. Jackson et al.
4. 4. Verbeke et al.
5. 5. Wang et al.
6. 6. Redis et al.