Creative Biolabs is a global company that focuses on messenger ribonucleic acid (mRNA) studies. With our extensive experience and advanced platform, we can provide a series of mRNA-based protein replacement therapy services based on state-of-the-art technologies. We are proud to partner with our clients on the journey of bringing novel mRNA-based protein therapies to the clinical application.
Proteins have been considered as key molecules in humans, and they have proven their significant roles in regulating physiological and biological reactions, protecting the human body from viral and bacterial infections. In the past few years of studies, a wide variety of human diseases have been associated with different proteins. Moreover, most natural and modified proteins have been generated by various advanced technologies, such as genetic engineering and protein engineering, to be further expressed by different systems, including phage display technology.
Also, therapeutic proteins have been broadly used for developing novel therapies against human diseases. Among them, protein replacement therapy has been used as an effective method for replacing the dysfunctional proteins or missing proteins in patients. For instance, pilot studies have demonstrated that replacing the defective collagen VII (C7) protein is essential to improve the performance of wound healing in patients with recessive dystrophic epidermolysis bullosa (RDEB). As a result, protein replacement therapy has become a potential therapy for a wide array of rare monogenic diseases, blood disorders, and metabolic disorders.
Fig.1 Disease classes targeted by protein replacement therapies.1
Currently, mRNA-based therapeutics has shown its great potential in the treatment of various human diseases, especially for malignant tumors. mRNA delivery systems have been regarded as safe and transient methods with a high transduction capacity in disease therapies. In recent studies, a new mRNA-based protein replacement therapy has been designed based on replacing the uridine residues in mRNA with nucleoside pseudouridine. The results have indicated that this therapy can interrupt innate immune responses caused by RNase and Toll-like receptors, reducing the expression level of various cytokines and avoiding the immunogenicity during treatment.
As a professional expert in the field of mRNA therapeutics development, Creative Biolabs offers a one-stop mRNA-based platform for our clients, to design and synthesize suitable mRNA constructs, to generate safe and effective mRNA-based protein replacement therapies, as well as to evaluate the properties of mRNA-based therapies by using a panel of immunoassays. Besides, the mode of delivery routes can be assessed by our labs to avoid protein metabolism or clearance before entering the target cells and tissues. For example, in vitro transcribed (IVT) mRNA has worked as a protein replacement therapy for the heart. The data has suggested that this mRNA therapy carrying VEGF-A into mice heart can strongly increase the survival rates (80% survival) of mice in different heart disease models. Up to now, several protein replacement therapies have been generated by our labs, and several of them have been used in many large scales of rare monogenic disease models.
Fig.2 An overview of IVT mRNA-based therapeutics.2
By continuing to grow in response to the requirements of our clients, Creative Biolabs is dedicated to exploring novel mRNA therapeutics to offer the most comprehensive, integrated portfolio of mRNA products and solutions. The members in our labs have originated from a rich academic research background, bringing their experience into practice. If you are interested in our services, please feel free to contact us for more information.
Inquire About Our ServicesA: RNA-based protein replacement therapy involves using messenger RNA to instruct cells to produce specific proteins that replace dysfunctional or missing proteins in the body. This method offers a transient and safe approach to treating diseases caused by protein deficiencies, such as rare monogenic disorders, by providing a temporary source of the needed protein.
A: Traditional protein replacement therapies often involve directly administering the protein to patients, which can be costly and less efficient. In contrast, mRNA-based therapy delivers mRNA that encodes the protein, allowing the patient's cells to produce the protein themselves, leading to potentially higher efficacy and reduced immunogenicity.
A: This therapy offers several advantages, including a lower risk of immune response, efficient and localized protein production, and the ability to quickly adapt to different proteins as needed. It also provides a more stable and controlled delivery method, with the mRNA being designed to optimize protein expression while minimizing potential side effects.
A: mRNA-based protein replacement therapy is particularly effective for treating rare monogenic diseases, metabolic disorders, and blood disorders where specific protein deficiencies are the underlying cause. It can also be applied in regenerative medicine and to improve outcomes in conditions like heart disease by promoting tissue repair through protein expression.
A: Creative Biolabs offers comprehensive services, including mRNA design, synthesis, delivery system development, and preclinical evaluation. They provide tailored solutions for each project, ensuring that the mRNA constructs are optimized for stability, expression, and safety, with rigorous testing to meet the therapeutic needs of each client.
A: Challenges include ensuring the stability of mRNA, avoiding degradation by RNases, controlling the immune response, and optimizing delivery to target cells. Creative Biolabs addresses these challenges through advanced mRNA modification techniques, careful design of delivery systems, and thorough preclinical testing.
A: Safety is ensured through the use of non-integrating mRNA, reducing the risk of insertional mutagenesis. Additionally, mRNA constructs are designed to minimize immune activation, and comprehensive preclinical studies are conducted to evaluate potential side effects and ensure the therapy is both effective and safe.
In this study, mRNA-based Protein Replacement Therapy was explored using a lipid nanoparticle (LNP) delivery system called LUNAR to treat hemophilia B, a genetic disorder caused by deficiency of coagulation factor IX (FIX). The therapy involved the systemic delivery of human FIX (hFIX) mRNA encapsulated in LUNAR LNPs into a mouse model of hemophilia B. The results showed that this delivery system effectively produced therapeutic levels of FIX protein in the liver, restoring normal clotting activity in the mice. The FIX protein remained stable for several days, providing a longer-lasting therapeutic effect. Additionally, the treatment was well-tolerated, with no significant adverse immune responses or liver toxicity observed, even with repeated administrations. This study demonstrates the potential of mRNA-based therapies as a viable and efficient alternative for protein replacement in genetic disorders like hemophilia B.
Fig.3 Comparison of the therapeutic effects between R338A FIX mRNA and recombinant human FIX protein.3
| Cat. No | Product Name | Promoter |
|---|---|---|
| GTVCR-WQ19MR | IVTScrip™ pT7-VEE-mRNA-Anti-H1-0, (131)I-chTNT-1/B Vector | T7 |
| GTVCR-WQ22MR | IVTScrip™ pSP6-VEE-mRNA-Anti-H1-0, (131)I-chTNT-1/B Vector | SP6 |
| GTVCR-WQ24MR | IVTScrip™ pT7-VEE-mRNA-Anti-KDR, 1121B Vector | T7 |
| GTVCR-WQ25MR | IVTScrip™ pSP6-VEE-mRNA-Anti-KDR, 1121B Vector | SP6 |
| GTVCR-WQ28MR | IVTScrip™ pT7-VEE-mRNA-Anti-EGFR, 11F8 Vector | T7 |
| Cat. No | Product Name | Type |
|---|---|---|
| GTTS-WQ15MR | IVTScrip™ mRNA-Anti-S, 2130(Cap 0, 5-Methyl-CTP & Pseudo-UTP, 120 nt-poly(A)) | Antibody |
| GTTS-WQ16MR | IVTScrip™ mRNA-Anti-S, 2130(Cap 1, 5-Methyl-CTP & Pseudo-UTP, 120 nt-poly(A)) | Antibody |
| GTTS-WQ17MR | IVTScrip™ mRNA-Anti-S, 2130(Cap 0, 5-Methyl-CTP & Pseudo-UTP, 30 nt-poly(A)) | Antibody |
| GTTS-WQ18MR | IVTScrip™ mRNA-Anti-S, 2130(Cap 1, 5-Methyl-CTP & Pseudo-UTP, 30 nt-poly(A)) | Antibody |
| GTTS-WQ19MR | IVTScrip™ mRNA-Anti-S, 2130(Cap 0, Pseudo-UTP, 120 nt-poly(A)) | Antibody |
References
