Dendrimer Development Service

Development of Dendrimers for Gene Delivery

Dendrimers have emerged as promising synthetic vectors for gene delivery. Our company aims to provide customers with one-stop services for the development of dendrimer-based gene delivery systems. We have established multiple strategies for customizing plain or chemically modified dendrimers to expand the potential of these vectors for gene therapy of rare diseases.

Background

Dendrimers consist of a central core, branches emanating from the core, and terminal functional groups, and have a high degree of geometric symmetry. As a result of their spherical shape, high density of surface functional groups, and controlled molecular structure, they are widely utilized in gene therapy as novel nucleic acid delivery technologies. Cationic dendrimers, such as polyamidoamine (PAMAM) dendrimers, poly(propyleneimine) dendrimers (PPI), and poly(L-lysine) dendrimers (PLL) have become important vectors for nucleic acid delivery.

Dendrimers possess the ability to condense nucleic acids through electrostatic interactions, which are responsible for the formation of nanoparticles, also known as dendritic complexes. Dendrimers have been shown to effectively complex different types of nucleic acids such as DNA, RNA, or oligodeoxynucleotide (ODN), often with higher transfection efficiency and lower toxicity than linear or branching polymers.

Fig. 1 Schematic representation of the PAMAM dendrimer modification strategies. (Tarach P, et al., 2021)

Our Services

Rational modification of dendrimers can be used to promote colloidal stability, enhance condensation capacity, and target nanostructures to desired cells in vivo. We provide a variety of methods to help customers prepare and modify (such as glycosylation, acetylation, or peptide modification) dendrimers to meet their different needs in the field of gene therapy.

Preparation of dendrimers
The synthesis of dendrimers is closely related to molecular and polymer chemistry. We help our customers to synthesize dendrimers for gene delivery through progressive and precisely controlled synthesis routes. The methods we provide include:
- Classical synthetic routes, including the divergent growth method and the convergent growth method.
- Efficient synthetic routes, including the double exponential growth method, double-stage convergent method, and the branched monomer approach.
Chemical modification of dendrimers
We focus on the modification of surface functional groups, central cores, dendrimer structures, and the assembly of low-generation dendrimers to help our customers overcome multiple barriers to gene delivery. Our modification strategies include:
- Modification of dendritic structures
  We offer the insertion of spacers (rigid or flexible) in the inner core and the thermal degradation of branches to achieve dendritic modifications.
- Modulation of DNA and biofilm interactions
  We regulate the screening of dendrimers for strong interactions with biological membranes by grafting PEG derivatives, acetylation of terminal amino groups, or insertion of hydroxyl groups. And we enhance gene condensation capacity by quaternization of internal or surface amino groups.
- Regulation of cellular uptake and trafficking
  We promote cellular internalization by insertion of targeting motifs (top), cyclodextrins, fusigenic peptides, or hydrophobic molecules (bottom).
Characterization of dendrimers
We offer a variety of characterization techniques to help customers specifically characterize the structure, shape, size, and morphological behavior of dendrimers and predict possible in vivo interactions. Our techniques include:
- Various spectrometric and spectroscopic methods such as mass spectrometry, X-ray diffraction, infrared spectroscopy, UV-Vis, and fluorescence spectroscopy
- Various microscopy techniques such as transmission electron microscopy and atomic force microscopy
- Various physical and rheological characterization methods and multiple scattering methods

With the above services, we offer a variety of dendritic polymers for your convenience.

PAMAM dendrimers
PAMAM has a multi-functional peripheral surface and the amino group is positively charged by protonation, which can easily bind to DNA to form nanoscale complexes for DNA protection and transfection purposes. We offer multiple generations of amine-terminated PAMAM dendrimers according to your different research demands.
Dendrigraft
We help our customers develop novel gene vectors composed of dendrigraft poly(l-lysine) (DGL). We provide multiple generations of DGLs functionalized with amine surface groups and offer a variety of strategies to improve the efficiency of gene transfection.
Dendrimers conjugated with biocompatible materials
We modified the dendrimers with multiple biocompatible materials to reduce toxicity and improve gene transfer activity. We provide dendrimers conjugated with PEG, dendrimers conjugated with cyclodextrins (CDs), and dendrimers conjugated with amino acids.

Our dedicated research team works on surface functionalization and charge improvement with a variety of modification strategies to help customers develop safe and effective dendrimer-based gene delivery vectors. With our expertise in gene therapy, we will tailor the most appropriate solution for your project. Please contact us for more details and to get a formal quote.

Reference

Tarach, P.; Janaszewska, A. Recent advances in preclinical research using PAMAM dendrimers for cancer gene therapy. International Journal of Molecular Sciences, 2021, 22(6): 2912.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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