The field of messenger RNA (mRNA) therapeutics is currently undergoing a major expansion, and the potential for using mRNA drugs for personalized medicine and immunotherapy as well as to address genetic, infectious, and chronic diseases will ensure the continued development of RNA therapeutics. However, the development of mRNA as a therapeutic faces the same challenge as any nucleic acid: delivery, delivery, delivery.
Experienced scientists at Creative Biolabs are glad to apply our special expertise to help our worldwide customers in the development of custom delivery systems (including lipid-based vectors, polymer-based vectors and hybrid vectors) for mRNA.
mRNA has several advantages over DNA for gene transfer and expression, including the lack of any requirement for nuclear localization or transcription and the nearly negligible possibility of genomic integration of the delivered sequence. After over two decades of development, mRNA has broad potential as a therapeutic. The design and chemistries used to synthesize mRNAs have advanced to a point where they enable adequate stability and immune evasion, while at the same time allowing the maintenance of efficacy and specificity. Current clinical efforts are focused on vaccination, protein replacement therapies, and treatment of genetic diseases. The clinical translation of mRNA therapeutics has been made possible through advances in the design of mRNA manufacturing and intracellular delivery methods.
Fig.1 Schematic representation of extra- and intracellular barriers for mRNA delivery. (Kowalski, 2019)
A desired mRNA delivery vehicle must include: 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) efficiently clearance of delivery vehicle components; 6) low toxicity. Although the delivery technologies have greatly progressed by the discovery of potent and bio-compatible materials, aided by high-throughput screening technologies, broad application of mRNA is still limited by the need for improved delivery systems.
mRNA is emerging as a highly versatile biological construct for the creation of impactful medicines. mRNA therapeutics directed toward infectious disease and cancer are in clinical development with encouraging early reads on tolerability and efficacy. The versatility of mRNA has created several unique opportunities for clinical application, each with unique delivery requirements.
Integrating cutting-edge platforms as well as substantial experience in the study of delivery vehicles for mRNA, Creative Biolabs is pleased to address the scientific and technical challenges in the development of custom delivery vehicles for mRNA. Our commonly used delivery vehicles for mRNA include but are not limited to:
Lipids and lipid-like materials represent the second major class of nanoparticle-based delivery vehicles for RNA. Cationic lipids are often used to electrostatically bind the nucleic acid while ionizable lipids are positively charged only in acidic environments, and this ionizable behavior is thought to enhance efficacy through helping with endosomal escape and reducing toxicity. Our scientists have accumulated rich experience in enhancing the stability and efficacy of lipid-based mRNA delivery systems. We are confident in providing clients with the best service at the most competitive cost.
Nanoparticle encapsulation physically protects mRNA from degradation and, depending on the specific chemistry, can aid in cellular uptake and endosomal escape. Given their high degree of chemical flexibility, polymers are commonly used materials for nanoparticle-based delivery. Creative Biolabs gathers lots of scientists who are proficient in the development of polymer-based mRNA delivery systems, mainly including polyplex and micelleplex.
The hybrid delivery system has shown promising results for the delivery of mRNA, with the mRNA being encapsulated in a hybrid nanoparticle composed of the lipid-like material with a polymeric PLGA core. The hybrid formulation is thermodynamically favorable, with respect to hydrophobic, van der Waal, and electrostatic interactions. Creative Biolabs is pleased to share our cutting-edge technology and extensive expertise in the development of hybrid mRNA delivery systems to facilitate our clients' research and project development.
mRNA therapeutics has become increasingly attractive due to recent advances in manufacture, scalability and cost. Creative Biolabs is more than happy to share our experience in the development of mRNA delivery systems to facilitate our clients' mRNA therapeutics projects. For more detailed information, please feel free to contact us or directly send us an inquiry.
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