Development of Dendrimers as Gene Delivery System
In order to avoid the immune response caused by viral vectors, scientists start averting their attention to non-viral vectors given their high efficiency and large insert capacity. Dendrimers are highly branched polymer-based macromolecules which have a spherical and symmetrical structure in precise size, and the terminal group function. Creative Biolabs has years of experience in providing gene therapy services, with multiple dendrimers available for your convenience.
Dendrimers contain three regions: a central core, branches emanating from the core, and terminal function groups. Dendrimers bind to genetic material for gene delivery. Because of their nanometric size, dendrimers can interact specifically and effectively with membranes and proteins. Here, we provide a variety of methods to functionalize the surface of the dendrimers to meet different demands of our worldwide customers.
Fig.1 The mechanism of dendrimer-mediated gene delivery into cells
PAMAM Dendrimers
PAMAM dendrimers are highly branched nanometer-sized polymers with a multifunctionalized peripheral surface, with a high degree of molecular uniformity, monomolecular weight as well as specific size and shape. PAMAM dendrimers are water soluble, biocompatible and can act as non-immunogenic gene delivery vectors. Amine-terminated PAMAM dendrimers have high density of positively charged terminal groups that show high cellular uptake. Creative Biolabs provides multiple generations (G0-G10) of amine-terminated PAMAM dendrimers for you to choose from based on your different research demands.
Fig.2 Representations of positively charged PAMAM dendrimers
Dendrigraft
Dendrigraft poly(l-lysine) (DGL) is a dendritic cationic polypeptide synthesized by a polycondensation reaction. DGLs have large and flexible structures and grow fast. In DGLs, the number of amine surface groups increases significantly as a function of generation. Free primary amines are abundant both on the surface and inside of the molecule. Creative Biolabs provides multiple generations (G2-G5) of DGLs with the amine surface group functionalization, and improves the efficiency of gene transfection by using histidine or imidazole to help complexes escape from the endosome.
Fig.3 Flow chart of the production of dendrigraft
Dendrimers conjugated with biocompatible materials
In order to eliminate the cytotoxicity of higher-generation dendrimers, scientists use specific molecules to functionalize the amine-terminal groups of dendrimers. We provide various biocompatible materials to modify the dendrimers to reduce toxicity and increase gene transfer activity.
- Dendrimer conjugated with PEG
The PEGylation of dendrimers offers many advantages, including better gene delivery, high transfection efficiency, low cytotoxicity and reduced immunogenicity both in vitro and in vivo.
- Dendrimer conjugated with CDs
Cyclodextrins (CDs) are a type of non-toxic and non-immunogenic oligosaccharide. PAMAM dendrimers with CDs synergize the proton sponge effect to promote the release of complexes in the cytosol.
- Dendrimers conjugated with amino acids
L-phenylalanine-modified dendrimers can enhance gene translocation to improve transduction efficiency.
Creative Biolabs has been committed to surface functionalization and charge improvement in a variety of ways to efficiently deliver DNA or RNA with little or no toxicity. We offer one-stop services about the development of dendrimers as a gene delivery system. Please feel free to contact us for more details and our scientists will tailor the most reasonable scheme for your projects.
Reference
- Hu, J.; et al. (2016). Tailoring the dendrimer core for efficient gene delivery. Acta biomaterialia, 35, 1-11.
