CpG incorporated DNA microparticles for elevated immune stimulation for antigen presenting cells

Abstract

As emerging evidence supports the immune stimulating capability of the CpG oligodeoxynucleotides (ODN), CpG-based adjuvants have been widely used.

Immunostimulatory Effects Triggered by Self‐Assembled Microspheres with Tandem Repeats of Polymerized RNA Strands

“…Meanwhile, the same amount of self‐assembled CpG DNA microsphere (DMS) made up of CpG ODN was also used as a control group, which was introduced in our previous study. [14a] As expected, dsRMS‐70 treated cells showed the highest expression of IFN‐β among all types of RMSs with the release of dsRNA fragments by systemic degradation after cellular uptake. Taken together, it was confirmed that the RMS with 70 bp long‐dsRNA region would be able to induce moderate immune response from RAW264.7 cells.…”

“…On the other hand, the immunogenicity of self‐assemblies composed of DNA, RNA, or DNA‐RNA hybrid has been investigated widely for the better understanding of immunogenic properties of nucleic acid‐based structures and their clinical translation. However, the study of immune stimulating properties of self‐assembled RNA particles with potentially immunostimulatory RNA fabricated from RCT is not well established, whereas DNA particles from rolling circle amplification have been widely exploited as adjuvants for boosting immune response . In order to clinically translate the fast‐evolving RNA‐based therapeutics, evaluation of immune response to self‐assembled RNA particles is indispensable.…”

“…The size of RMSs enabled an effective internalization by macrophages without further complexation as reported previously. [14a] However, the RMSs showed minimal or negligible immunostimulatory effect on the cells regardless of the presence of CpG content and degree of double‐stranded structure without systemic release of RNA fragments. To the best of our knowledge, this is the first report suggesting the application of self‐assembled RNA‐based particles should not be limited by potential immunotoxicity.…”

“…This indicates that ssRMSs have a favorable size to be phagocytosed by macrophages (Figure b). [14a,18] According to SEM and TEM images, the porous structures of ssRMS were observed with a highly packed internal structure (Figure b, inset). The dsRMSs also showed spongelike spherical structure with an average diameter of 1.8 µm with the PDI value of 0.243 which could also be engulfed by macrophages (Figure c,d and Figure S1b, Supporting Information).…”

Small Molecule NF-κB Inhibitors as Immune Potentiators for Enhancement of Vaccine Adjuvants

“…To broadly establish how the addition of these inhibitors impacts the antibody levels, we chose to analyze the total Ig (G+A+M) produced after 21 days ( 18 ). On day 21, we analyzed the anti-OVA antibody levels ( Figure 1D ).…”