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 bench to 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 are a highly customizable nucleic acid delivery vector that has shown immense potential in mRNA vaccines. They are a multi-component system made up of four lipid components: ionizable or cationic lipids, phospholipids, polyethylene glycol lipids, and cholesterol. Its production relies on the ability of self-assembly, that is, the spontaneous organization of lipid components into nanostructured entities based on intermolecular interactions. In addition to mRNA vaccinations, LNPs are commonly employed in gene editing and rare illness gene therapy. They can also conjugate specific compounds for in vivo tissue-specific delivery.
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.
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.
Fig.1 Schemes of lipid-based formulations, including LP, lipopolyplex (LPR), LNP and CNE.1
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 customers' needs from early research to commercial production. Please contact us for more information and a detailed quote.
A: Lipid-based vectors are specialized systems used to encapsulate and deliver mRNA into target cells efficiently. These vectors typically consist of lipid nanoparticles (LNPs) designed to protect mRNA from degradation, facilitate cellular uptake, and promote endosomal escape, ensuring that the mRNA reaches the cytoplasm where it can be translated into proteins.
A: Creative Biolabs offers an array of services for the development and optimization of lipid-based vectors for mRNA delivery. These services include LNP formulation and optimization, encapsulation efficiency assessment, in vitro and in vivo delivery efficiency testing, stability analysis, and custom design of lipid-based vectors tailored to specific research needs or therapeutic applications.
A: Creative Biolabs utilizes advanced techniques and comprehensive optimization strategies to enhance the efficiency of lipid-based vectors. This involves adjusting the composition of lipids, optimizing particle size and charge, improving encapsulation efficiency, and testing various formulations to achieve the highest delivery efficiency and biocompatibility for the target application.
A: Lipid-based vectors offer several advantages for mRNA delivery, including high encapsulation efficiency, protection of mRNA from enzymatic degradation, efficient cellular uptake, and promotion of endosomal escape. Additionally, they can be customized to target specific cells or tissues, enhancing the specificity and effectiveness of mRNA-based therapies or research applications.
A: Yes, Creative Biolabs provides comprehensive assessment services to evaluate the delivery efficiency of lipid-based vectors. This includes in vitro assays to measure cellular uptake and protein expression, as well as in vivo studies to assess biodistribution, targeting efficiency, and therapeutic efficacy in relevant animal models.
A: Creative Biolabs can encapsulate a wide range of mRNA types using lipid-based vectors, including synthetic mRNA, modified mRNA, self-amplifying RNA, and therapeutic mRNA encoding for proteins, peptides, or other biomolecules. They tailor the formulation process to ensure optimal delivery and functionality of the specific mRNA being used.
A: Creative Biolabs stands out due to their extensive expertise in lipid chemistry and mRNA delivery technologies, state-of-the-art laboratory facilities, and commitment to personalized service. Their tailored approach, robust quality control measures, and dedication to innovative solutions ensure that researchers and developers receive high-quality, effective vector systems for their mRNA delivery needs.
In this study, lipid-based vectors, specifically Lipofectamine and ionizable lipid nanoparticles (i-LNPs), were examined for their efficiency in mRNA delivery and subsequent protein expression. Using live-cell imaging and single-cell arrays, the researchers found that Lipofectamine-mediated delivery was less efficient and exhibited longer delivery times with increasing serum concentration. Conversely, i-LNPs demonstrated higher efficiency and faster uptake in the presence of serum. This work illustrates the variance in delivery timing and protein expression rates at the single-cell level, providing insights into the uptake and release mechanisms of these vectors, crucial for enhancing the performance of RNA-based therapeutics.
Fig.2 Protein adsorption on the nanocarrier's surface has the opposite effect on ionizable lipid nanoparticles i-LNPs compared to lipoplexes.2
| Cat. No | Product Name | Promoter |
|---|---|---|
| CAT#: GTVCR-WQ001MR | IVTScrip™ pT7-mRNA-EGFP Vector | T7 |
| CAT#: GTVCR-WQ002MR | IVTScrip™ pT7-VEE-mRNA-EGFP Vector | T7 |
| CAT#: GTVCR-WQ003MR | IVTScrip™ pT7-VEE-mRNA-FLuc Vector | T7 |
| CAT#: GTVCR-WQ87MR | IVTScrip™ pT7-VEE-mRNA-Anti-SELP, 42-89-glycoprotein Vector | T7 |
| Cat. No | Product Name | Type |
|---|---|---|
| CAT#: GTTS-WQ001MR) | IVTScrip™ mRNA-EGFP (Cap 1, 30 nt-poly(A)) | Reporter Gene |
| CAT#: GTTS-WK18036MR | IVTScrip™ mRNA-Human AIMP2, (Cap 1, Pseudo-UTP, 120 nt-poly(A)) | Enzyme mRNA |
| (CAT#: GTTS-WQ004MR) | IVTScrip™ mRNA-Fluc (Cap 1, 30 nt-poly(A)) | Reporter Gene |
| (CAT#: GTTS-WQ009MR) | IVTScrip™ mRNA-β gal (Cap 1, 30 nt-poly(A)) | Reporter Gene |
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