Oligonucleotide delivery to antigen presenting cells by using schizophyllan

Area of Science:

• Biochemistry
• Immunology
• Materials Science

Background:

• Schizophyllan (SPG), a beta-glucan, forms complexes with polynucleotides like poly(dA) via hydrogen bonding.
• Dectin-1, a key beta-glucan receptor, is expressed on antigen-presenting cells (APCs) such as macrophages and dendritic cells.

Purpose of the Study:

• To investigate the potential of SPG-polynucleotide complexes for delivering functional oligonucleotides (ODNs) to APCs.
• To evaluate the therapeutic efficacy of SPG-ODN complexes in disease models and their ability to modulate immune responses.

Main Methods:

• Complex formation between SPG and poly(dA) was analyzed.
• Quartz crystal microbalance was used to assess the binding of SPG-dA60 complexes to recombinant Dectin-1 protein.
• Therapeutic efficacy was tested using antisense (AS)-ODN complexes in a mouse model of hepatitis.
• Immune responses were evaluated after immunization with CpG-ODN/SPG complexes and antigenic proteins.

Main Results:

• SPG forms complexes with poly(dA) that are recognized by Dectin-1.
• An AS-ODN/SPG complex protected mice against LPS-induced hepatitis at a low therapeutic dose.
• CpG-ODN/SPG complexes combined with antigenic proteins induced potent antigen-specific immune responses.
• SPG-DNA complexes facilitate peptide delivery and nanogel formation.

Conclusions:

• Beta-glucan-based complexes offer a novel strategy for delivering specific ODNs to APCs.
• These complexes hold promise for treating diseases involving APCs and for activating antigen-specific immunity.