Nucleic acid therapeutics need hybrid vectors to overcome cytoplasmic delivery inefficiency, systemic clearance, and low specificity. Hybrid systems combine lipids' biocompatibility with polymers/peptides' structural control, solving stability, targeting, and endosomal escape issues.
Creative Biolabs offers custom hybrid vector development via advanced core-shell nano-architecture and AI-driven optimization. It engineers tailored nanocarriers for your cargo and target, turning unreliable payloads into clinically viable candidates.
Creative Biolabs specializes in delivering two highly effective types of hybrid vectors, each offering unique performance characteristics for distinct therapeutic goals.
A Lipopolyplex is a ternary charge-based self-assembled core-shell complex—its core has negatively charged nucleic acid (mRNA) condensed with a cationic polymer (polyplex), enveloped by a lipid shell; this architecture offers dual protection (polymeric core ensures mRNA stability and drives endosomal escape, lipid shell minimizes immunogenicity and enhances cell uptake.
Cationic Nanoemulsions are flexible hybrid carriers that use charge-based self-assembly, combining lipids, polymers, surfactants, co-surfactants and cationic agents; they offer thermodynamic stability and high payload capacity (liquid core stabilizes large payloads like saRNA), cationic components enable strong nucleic acid binding with low viscosity for sterile filtration, and Creative Biolabs uses advanced techniques to control droplet size and surface charge for superior stability and effective cellular uptake across cell types.
Tab.1 Hybrid Vector Types for mRNA Delivery.
| Hybrid Vector Type | Core Design Principle | Typical Application Scenarios |
|---|---|---|
| Lipid-Polymer Hybrid Vector | Cationic polymer (e.g., PEI, PBAE) as a core to condense mRNA; lipid layer (ionizable/helper lipids) for surface modification or wrapping. | Systemic mRNA delivery (e.g., liver, lung targeting) |
| Virus-Lipid Hybrid Vector | Virus/VLP as base, modified with lipid membrane or PEG-lipids; or fuses viral functional elements (e.g., envelope proteins) with LNPs. | mRNA delivery to hard-to-transfect cells (e.g., DCs, neurons) for cancer immunotherapy |
| Virus-Polymer Hybrid Vector | Virus particles wrapped in biocompatible polymers (e.g., PEG, PLGA) or polymers conjugated with viral targeting elements. | Repeated mRNA administration (e.g., long-term gene regulation for chronic diseases) |
| Inorganic Nanomaterial-Lipid/Polymer Hybrid Vector | Inorganic nanoparticle (e.g., AuNP, MSN) as a stable scaffold; surface modified with lipid/polymer to load mRNA. | Local mRNA delivery (e.g., skin, tumor site targeting); enhanced cancer immunotherapy via photothermal-triggered release |
| Peptide-Lipid/Polymer Hybrid Vector | Functional peptides (e.g., targeting peptide RGD, CPP TAT, endosomal escape peptide) conjugated to lipid/polymer carriers. | Tissue-specific mRNA delivery (e.g., tumor, muscle, liver); liver disease treatment via GalNAc peptide-modified vectors |
Required Starting Materials:
| Stage | Activity Description |
|---|---|
| Rational Design & Modeling | Utilize our proprietary AI-driven algorithms to model and predict the optimal physicochemical parameters (pKa, material ratios, particle size) of the hybrid vector core and shell, tailored to the required cargo and target. |
| Component Synthesis & Assembly | Chemically synthesize novel polymer and lipid components (if required) and assemble the lead candidates into core-shell hybrid nanoparticles using controlled techniques such as microfluidics. |
| Physicochemical Characterization | Rigorously analyze key properties, including particle size (DLS), zeta potential, morphology (TEM/Cryo-EM), and encapsulation efficiency, ensuring payload protection and colloidal stability. |
| Biological Validation (In Vitro) | Test vector stability against serum nucleases, measure cellular uptake kinetics, and quantify endosomal escape efficiency and final transfection or knockdown rates in the specified target cell model. |
| In Vivo Efficacy Consultation | Based on in vitro success, advise on optimal administration route and dose. If requested, initiate preclinical in vivo studies to assess biodistribution, immune response, and therapeutic expression in animal models. |
Final Deliverables:
Estimated Timeframe: The typical timeframe for this service ranges from 8 to 14 weeks, depending on the initial complexity of the cargo and the depth of the in vivo validation required.
Discover How We Can Help - Request a ConsultationOur Hybrid Vector Development Services are built on three pillars: customization, precision, and scalability, providing unparalleled control over your genetic therapeutic project.
Custom Core-Shell Optimization
Tailored development of Lipopolyplexes and Cationic Nanoemulsions with specific ionizable lipid and polymeric component ratios to precisely match your unique nucleic acid cargo (mRNA, siRNA, saRNA).
Guaranteed Endosomal Escape Efficiency
Engineering of vectors with pH-responsive polymer cores to ensure high-yield cytoplasmic release, overcoming the most challenging barrier of non-viral delivery with scientifically proven mechanisms.
Enhanced Targeted Delivery
Capabilities for surface functionalization with custom ligands (peptides, aptamers) to achieve precise tissue tropism and cellular specificity in vivo, minimizing off-target effects.
Seamless Scalability & Quality
Implementation of a Quality-by-Design (QbD) approach with controlled microfluidics technology to ensure process reproducibility and a clear path toward large-scale, GMP-compatible manufacturing.
Comprehensive QC & Data Package
Provision of detailed physicochemical, stability, and in vivo biodistribution data, ensuring your therapeutic candidate meets all necessary criteria for regulatory readiness.
Z-Average
Fig.1 The Z-average values of the hybrid nanoparticles were detected by dynamic light scattering experiments.1
Encapsulation Efficiency
Fig.2 The detection was conducted at the same 2.5:1 PHA: lipid ratio (%wt) and different polymer lipid encapsulation rates.1
Stability Testing
Fig.3 Detect the stability of hybrid nanoparticles under different temperatures and 8.8% sucrose solution conditions.1
Detection of Transfection Efficiency
Fig.4 To detect the transfection effect of lipid polymer hybrid nanoparticles (LPHNPs).1
A: While LNPs are effective, our Hybrid Vectors offer enhanced control. Standard LNPs rely primarily on lipid composition for endosomal escape. Hybrid systems add a functional polymeric core that is specifically engineered for pH-responsive destabilization, resulting in a more robust and predictable release of the payload into the cytoplasm.
A: Our platforms are versatile. We successfully formulate and deliver a wide range of nucleic acids, including mRNA, self-amplifying RNA (saRNA), small interfering RNA (siRNA), and plasmid DNA (pDNA). The flexibility of the hybrid architecture allows us to custom-adjust component ratios to accommodate varying sizes and rigidity of the cargo.
A: Absolutely. Our core-shell design is highly conducive to targeting. The lipid shell or polymeric surface can be readily functionalized with targeting ligands (e.g., peptides, antibodies, aptamers) without compromising particle stability. This capability is essential for achieving the precise tissue tropism required for advanced gene therapies.
A: Safety is paramount. Hybrid Vectors are non-viral, eliminating the risks associated with immunogenicity, random genomic integration, and manufacturing scale-up complexity inherent to viral vectors. Our advanced designs are optimized for low innate immune response while maintaining therapeutic potency.
A: We use a diverse, proprietary library of materials, typically including ionizable cationic lipids, helper lipids (like DOPE or cholesterol derivatives), PEG-lipids for circulation longevity, and carefully selected biodegradable cationic polymers (such as PEI derivatives or synthetic polypeptides) for the core. The precise combination is determined by the AI modeling stage to ensure peak performance for your application.
Creative Biolabs' Hybrid Vector Development is your strategic partner for advancing nucleic acid therapeutics. We provide rational design, cutting-edge Lipopolyplex and Cationic Nanoemulsion platforms, and AI-accelerated development to deliver highly stable, efficient, and targetable carriers. We solve the delivery challenge so you can focus on the cure.
Contact Our Team for More Information and to Discuss Your Project| 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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