Circular mRNA: The Next Generation of Personalized Medicine

Thailand’s Circular mRNA Research Faces Funding Hurdle, Seeks Investor Spotlight

Bangkok, Thailand – While Thailand possesses the foundational research and a prototype for Circular mRNA technology, a critical funding gap threatens to stall its growth and relegate the nation to relying on expensive foreign imports. This promising biotechnology, capable of revolutionizing disease treatment and research, requires significant investment to progress from laboratory experiments to human trials, according to Professor Suradet.

The article highlights that even though local support from entities like TISCO Bank exists, the ample budget needed for advanced research, notably clinical trials, remains a significant obstacle. Professor Suradet emphasizes that research is a collaborative effort, requiring a team of 20-30 medical scientists and experts. While modern technology has accelerated research timelines from two decades to potentially five to ten years, the absence of adequate capital will impede progress and force Thailand to procure costly technologies from abroad in the future.

Thailand’s potential in this field is underscored by its ability to develop Circular mRNA technology independently. The initial “upstream” investment for research per disease is estimated at a modest 10-20 million baht, with the potential for substantial returns of 200-300 million baht or more upon success. As a tangible example, the article points to CAR T-Cell technology, which Thailand can produce domestically for approximately 500,000 baht, a stark contrast to the 15 million baht cost of foreign copyrights.

“Circular mRNA is not merely a technology; it is an opportunity for the nation,” stated Professor Suradet. He urged Thai investors to recognize the potential of “watershed investments.” While the success of such ventures may not be instantly certain, a triumphant outcome promises to unlock immense value and ensure Thai citizens have access to life-saving treatments at affordable prices. He cautioned that without domestic support for homegrown research, thailand will be ill-equipped to respond to future disease crises, lacking the necessary technological capabilities. Ultimately, Circular mRNA represents not just scientific advancement but also a crucial element of public health and national pride.A Call for Support: Cancer Fund in Children Under Patronage

In a related initiative, the article also draws attention to the “Cancer Fund in Children under the patronage,” which has been supporting children with cancer for over two decades. This fund provides crucial assistance for treatment costs, medication, travel expenses, and medical supplies for disadvantaged young cancer patients. Donations can be made to the “Cancer Fund in Children under the patronage” at SCB On Nut Branch, account number 133-2-08742-3, or by calling 0-2718-3800 ext. 123. Receipts are eligible for tax deductions.Further details can be found at http://www.thaichildrencancerfund.org/.

The article is attributed to Prof. (Special) Dr. Pharmacist Abhisit Chattakonnon, a committee member of the Cancer Fund in Children under the patronage.

How does the circular structure of circular mRNA contribute to its enhanced stability compared to linear mRNA?

Understanding the limitations of Linear mRNA

For years, messenger RNA (mRNA) technology has held immense promise in medicine, notably with the rapid development and deployment of mRNA vaccines during the COVID-19 pandemic. However, traditional, linear mRNA faces inherent limitations. These include:

Rapid Degradation: Linear mRNA is quickly broken down by ubiquitous enzymes called RNases within the body, limiting its therapeutic effect.This necessitates higher doses and repeated administrations.

Immune Response: The body can recognize linear mRNA as foreign, triggering an unwanted innate immune response that can reduce efficacy and cause side effects.

Delivery Challenges: Efficiently delivering linear mRNA to target cells remains a significant hurdle,often requiring complex and possibly toxic lipid nanoparticles.

These challenges have spurred research into innovative mRNA designs, leading to the emergence of circular mRNA – a potentially revolutionary advancement in personalized medicine.

What is Circular mRNA?

Circular mRNA differs fundamentally from its linear counterpart in its structure. Instead of having free 5′ and 3′ ends, circular mRNA forms a covalently closed loop. This seemingly simple change has profound implications for its stability, translation efficiency, and immunogenicity.

Enhanced Stability: The circular structure protects the mRNA from degradation by RNases,dramatically increasing its half-life within cells. This translates to a longer-lasting therapeutic effect.

Reduced Immunogenicity: The absence of free ends reduces the recognition of circular mRNA as foreign by the immune system, minimizing unwanted inflammatory responses.

Improved Translation: Circular mRNA exhibits enhanced ribosome occupancy and prolonged translation, leading to increased protein production from the same amount of mRNA.

Sustainable Production: Circular mRNA can be produced using enzymatic circularization techniques, offering a potentially more scalable and cost-effective manufacturing process.

Production Methods for Circular mRNA

Several methods are currently employed to generate circular mRNA:

1. Enzymatic Circularization: This involves using RNA ligases to join the 5′ and 3′ ends of a linear mRNA precursor. this is currently the most widely used method.
2. In Vitro Transcription with Circular templates: Utilizing circular DNA templates during in vitro transcription directly produces circular mRNA.
3. Spliceosome-Mediated Circularization: Harnessing the cellular splicing machinery to create circular mRNA from specifically designed precursor RNA.

Each method has its advantages and disadvantages regarding efficiency,scalability,and cost. Ongoing research focuses on optimizing these techniques for large-scale production.

Applications in Personalized Medicine

The unique properties of circular mRNA open doors to a wide range of personalized medicine applications:

Cancer Immunotherapy: Circular mRNA encoding tumor-associated antigens can be delivered to stimulate a targeted immune response against cancer cells. The increased stability and reduced immunogenicity are particularly advantageous in this context.

Protein Replacement Therapy: For genetic disorders caused by deficient proteins, circular mRNA can provide a sustained source of the missing protein, potentially reducing the frequency of treatment. Examples include cystic fibrosis and muscular dystrophy.

Gene Editing: Circular mRNA can deliver CRISPR-Cas9 components for precise gene editing, offering a safer and more efficient alternative to viral vectors.

Vaccine Development: Circular mRNA vaccines demonstrate enhanced immunogenicity and durability compared to linear mRNA vaccines, potentially leading to more effective protection against infectious diseases.

Regenerative Medicine: Delivering circular mRNA encoding growth factors or other regenerative proteins can promote tissue repair and regeneration.

Circular mRNA vs. Linear mRNA: A comparative Table

| Feature | Linear mRNA | Circular mRNA |

|—|—|—|

| Structure | Open ends | Closed loop |

| Stability | Low | High |

| Immunogenicity | High | Low |

| Translation Efficiency | Moderate | High |

| Degradation Rate | Fast | Slow |

| Delivery | Requires complex nanoparticles | Potentially simpler delivery |

Real-World Examples & Clinical Trials

While still in relatively early stages of development, several companies are actively pursuing circular mRNA technology.

Circular Therapeutics: Focused on developing circular mRNA therapeutics for various diseases, including cancer and genetic disorders.

HyVacc: pioneering circular mRNA vaccine technology, demonstrating promising results in preclinical studies.

Moderna: Expanding its mRNA platform to include circular mRNA designs, exploring its potential for improved vaccine and therapeutic applications.

Currently, several Phase I and Phase II clinical trials are underway evaluating the safety and efficacy of circular mRNA-based therapies for various indications.Early data suggests promising tolerability and therapeutic potential.

Benefits of Circular mRNA Technology

Lower Doses: Increased stability and translation efficiency allow for lower doses, reducing potential side effects and manufacturing costs.

Reduced administration Frequency: Longer-lasting therapeutic effect minimizes the need for frequent administrations.

Enhanced Safety Profile: Reduced immunogenicity translates to a safer therapeutic experience.

Improved efficacy: Increased protein production and sustained expression lead to improved therapeutic outcomes.

Versatility: Applicable to a wide range of diseases and therapeutic modalities.

Future Directions and Challenges

Despite its immense potential, several challenges remain in the development of circular mRNA technology:

* Scalable Manufacturing: Optimizing production methods for large-