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Synthetic Cationic Glycopolymer Development Service

Development of Synthetic Cationic Glycopolymers for Gene Delivery

The synthesis of cationic glycopolymers and the study of their gene delivery profiles have been the focus of intensive research in the field of gene therapy for over ten years. Our company is committed to the design and synthesis of cationic glycopolymers to help customers develop carbohydrate-based vectors for gene delivery, accelerating progress in the field of gene therapy for rare diseases.

Background

The development of biocompatible, non-toxic, and highly effective gene delivery vectors holds great promise for curing many genetic and rare diseases. Modification of cationic polymers with sugar residues to generate cationic glycopolymers is an attractive strategy for introducing physiological stability into cationic polymers. Novel carbohydrate-containing polymeric vectors, termed glycopolymers, offer the advantages of enhanced biocompatibility, colloidal stability, and tissue-specific targeting. The development of these polymers has largely advanced the field of gene therapy.

Advances in chemistry and polymer chemistry have provided facile synthesis methods with ideal yields to produce cationic glycopolymers with well-defined and desired morphologies, allowing for the determination of structure-activity relationships. This information on structure-activity relationships has significance for the development of efficient polymer-based gene delivery vectors for non-viral gene therapies and gene editing technologies such as CRISPR/Cas9.

Fig. 1 (A) Structure of MAGalNAc-based diblock glycopolymers. (B) Plasmid-based polyplexes formed with MAGalNAc diblock copolymers promote the transfection of mouse liver tissue.

Fig. 1 (A) Structure of MAGalNAc-based diblock glycopolymers. (B) Plasmid-based polyplexes formed with MAGalNAc diblock copolymers promote the transfection of mouse liver tissue. (Van Bruggen C, et al., 2019)

Our Services

Our researchers have studied in detail the type of sugar moiety, degree of glycosylation, hydroxyl stereochemistry, DNA condensation efficiency, and DNA release to develop efficient cationic glycopolymer-based gene delivery vectors. We assist customers in the preparation of a wide range of well-controlled cationic glycopolymers of various molecular weights, shapes, structures, and cationic to carbohydrate contents through multiple methods, such as condensation polymerization, living radical polymerization, and post-polymerization conjugation. Furthermore, we offer a variety of optimization strategies to modify the structure and composition of these glycopolymers to optimize their ability to effectively transfect cells. We offer the following services to support our customers' research:

  • Development of poly(glycoamidoamine)s (PGAA)s
    PGAA and its analogs are usually synthesized from oligoethyleneamines containing 1 to 4 protonated secondary amines. In addition, we also provide the optimization service of the PGAA, such as using ring-closed monosaccharides and improving polyplex/cell contact through improved transfection methodology.
  • Development of block copolymers
    We help our customers prepare diblock copolymer structures consisting of a cationic block and a hydrophilic block to enhance colloidal stability and tissue targeting of polyplexes. We prepare carbohydrate-based block copolymers with well-defined composition and molar mass primarily through reversible addition-fragmentation chain transfer (RAFT) polymerization with vinyl monomers. Moreover, we further optimized these polymers, such as 2-deoxy-2-methacrylamido glucopyranose (MAG) and N-acetyl-d-galactosamine (GalNAc) block copolymers by assessing the effects of amine substitution, block length, composition, and structure on gene delivery efficiency.
  • Development of trehalose
    The incorporation of the disaccharide trehalose has been proven to improve the colloidal stability and cryostability of gene delivery vectors. We provide two polymerization techniques, including step-growth and chain-growth to help customers develop new trehalose-containing gene delivery vectors.

As a company focused on rare diseases, our team has made many efforts to advance non-viral gene therapy in rare diseases through the development of new cationic glycopolymer-based delivery vehicles via chemical synthesis techniques. If you require technical support and services for the development of carbohydrate-based nucleic acid delivery platforms, please contact us for more details and to get a formal quote.

Reference

  • Van Bruggen, C.; et al. Nonviral gene delivery with cationic glycopolymers. Accounts of Chemical Research, 2019, 52(5): 1347-1358.

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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