The ﬁeld of messenger RNA (mRNA)-based therapeutics spans from protein replacement therapy and gene editing to vaccination. However, the multifarious obstacles associated with mRNA's extremely large size, charge, intrinsic instability, and high susceptibility to enzymatic degradation hamper the translation of mRNA-based therapeutics from the bench to the bedside. Therefore, the wider application of mRNA-based therapeutics is still limited by the need for improved drug delivery systems.
Creative Biolabs has established a cutting-edge platform by integrating state-of-the-art technologies as well as substantial experience and expertise in the design and development of Custom Delivery Vehicle Vectors for mRNA. With proven experience in the research of lipid-based vectors for mRNA delivery, Creative Biolabs is an ideal company to be entrusted with your business.
Lipid-based vectors are among the most widely used non-viral nucleic acids carriers. The main component of lipidic systems is cationic lipids, which usually form lipoplexes by interacting with mRNA through electrostatic interactions. Lipoplexes enter the cell mainly via clathrin-mediated endocytosis (CME), or fusion with the cell membrane when in comparison polyplexes, via caveolae-mediated endocytosis (CvME). Their task is to protect mRNA against enzymatic hydrolysis.
LNPs include liposomes and other lipid-based nanoparticles, and they are regarded as one of the most developed systems for mRNA delivery. Currently, several LNP platforms are at the forefront of clinical trials. Indeed, they are clinically validated delivery systems for RNA therapy. In the beginning, LNPs were considered promising for the delivery of siRNA. The previous experience in siRNA formulation is beneﬁting the development of mRNA nanosystems, although mRNA has a diﬀerent structure which may interfere with the packing capacity of nanoparticles. For an optimal mRNA release, the delivery systems should contain less ionizable lipid and cholesterol but more phospholipid and polyethylene glycol (PEG) than in the case of siRNA.
CNE consists of a dispersion of an oil phase stabilized by an aqueous phase containing the cationic lipid. These nanoemulsions present a droplet size distribution of about 200 nm, and are mainly used to formulate mRNA vaccines. For example, a self-amplifying RNA (SAM) vaccine, expressing Human Immunodeﬁciency Virus (HIV) type 1 envelope, formulated in a CNE induced potent immune responses in rhesus macaques. Moreover, another well-tolerated and immunogenic SAM vaccine based on CNEs elicited immune responses in a variety of animal models (including mice, rats, rabbits, and nonhuman primates) at low doses.
Fig.1 Schemes of lipid-based formulations, including LP, lipopolyplex (LPR), LNP and CNE. (Midoux, 2015)
Lipidoids, which comprise multiple hydrophilic groups and several lipid tails, were developed in 2008 as novel siRNA delivery agents. Based on the encouraging results of siRNA delivery agents, zwitterionic amino lipids (ZALs), a new class of lipid-like materials, have been used for mRNA gene editing. Studies have shown that co-delivery of Cas9 mRNA and targeted sgRNA in a single ZAL nanoparticle enabled CRISPR/Cas9 gene editing in mice.
NLCs are another type of LNPs used to deliver mRNA for vaccination. NLCs are colloidal structures comprised of a core containing a mixture of solid and liquid lipids, resulting in an unstructured lipid matrix. A featured advantage of NLCs is the low toxicity respect to other lipid systems, such as emulsions, which require high quantities of surfactants and cosurfactants. Additionally, production and sterilization of NLCs are easy and cheap compared to other systems. A recent study has shown that administration of replicating viral mRNA encoding Zika virus antigens formulated in NLCs successfully protected mice against Zika virus infection.
Continued advancement in mRNA formulation and delivery using diﬀerent nanomaterials can improve the wider use of mRNA for the treatment and prevention of infectious diseases and cancers. Equipped with world-leading technology platforms and professional scientific staff in the field of mRNA delivery, Creative Biolabs offers high-quality custom LP/LNP services to meet our clients' demands precisely.
Creative Biolabs is glad to apply our expertise to help our worldwide customers in the development of lipid-based vectors. We are confident that our technology will meet customer's needs from early research to commercial production. Please contact us for more information and a detailed quote.