Increased immunostimulatory activity of polypod-like structured DNA by ligation of the terminal loop structures

Mohri, Kunihiko; Takahashi, Natsuki; Nishikawa, Makiya; Kusuki, Eri; Shiomi, Tomoki; Takahashi, Yuki; Takakura, Yoshinobu

doi:10.1016/j.jconrel.2012.08.001

Cited by 16 publications

(10 citation statements)

References 27 publications

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“…The extracellular immunostimulatory efficacy of RNA polygons was evaluated by measuring the release of cytokines TNF-α and IL-6 after addition to mouse macrophage-like RAW 264.7 cells (Figure 5A and B), as previously described (56,57). The triangular RNA nanoparticle coupled with only one CpG exhibited the highest level of cytokine induction for both TNF-α and IL-6 compared to square and pentagonal RNA nanoparticles.…”

Section: Resultsmentioning

confidence: 94%

Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles

Khisamutdinov

Jasinski

et al. 2014

Nucleic Acids Research

128

191

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Modulation of immune response is important in cancer immunotherapy, vaccine adjuvant development and inflammatory or immune disease therapy. Here we report the development of new immunomodulators via control of shape transition among RNA triangle, square and pentagon. Changing one RNA strand in polygons automatically induced the stretching of the interior angle from 60° to 90° or 108°, resulting in self-assembly of elegant RNA triangles, squares and pentagons. When immunological adjuvants were incorporated, their immunomodulation effect for cytokine TNF-α and IL-6 induction was greatly enhanced in vitro and in animals up to 100-fold, while RNA polygon controls induced unnoticeable effect. The RNA nanoparticles were delivered to macrophages specifically. The degree of immunostimulation greatly depended on the size, shape and number of the payload per nanoparticles. Stronger immune response was observed when the number of adjuvants per polygon was increased, demonstrating the advantage of shape transition from triangle to pentagon.

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Section: Resultsmentioning

confidence: 94%

Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles

Khisamutdinov

Jasinski

et al. 2014

Nucleic Acids Research

128

191

View full text Add to dashboard Cite

show abstract

“…This trend should continue for the foreseeable future as many classes of new materials have yet to be studied in depth and may have great potential in this field. Examples include DNA nanostructures that can present complex, three-dimensional multivalent motifs to engage and organize immune cell receptors 344–346 , nanoparticles with the capacity to embed within or penetrate cell membranes 347,348 , and novel self-assembling materials that can form complex, hierarchical nanoparticles. 349–351 While still in its infancy, the field of immune engineering, with nanoparticle technologies as key tools, is moving rapidly with a number of technologies moving beyond small animal models to non-human primate testing or other large animal models and small early-stage clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Synthetic Nanoparticles for Vaccines and Immunotherapy

Irvine

Hanson²,

Rakhra³

et al. 2015

Chem. Rev.

665

566

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“…Hexapodna containing GpC dinucleotide (GpC hexapodna-1) was used as model DNA. The migration of GpC hexapodna-1 slowed with increased addition of ED 7 -OVA or ED 17 -OVA ( Figure 1 a-c). By contrast, the addition of OVA had little impact on the migration of GpC hexapodna-1.…”

Section: Cationized Ova Formed a Complex With Dna And Was Gradually Rmentioning

confidence: 97%

“…Table 1 summarizes the number of modifi ed carboxyl groups and the net charge of ethylenediamine (ED)-conjugated OVAs (ED-OVAs). The average number of modifi ed carboxyl groups was 7.3 and 16.7 for ED 7 -OVA and ED 17 -OVA, respectively. The net charge, estimated from the amino acid composition and the degree of modifi cation, was positive for both ED-OVA derivatives.…”

Section: Introductionmentioning

confidence: 99%

Induction of Potent Antitumor Immunity by Sustained Release of Cationic Antigen from a DNA‐Based Hydrogel with Adjuvant Activity

Umeki

Mohri

Kawasaki

et al. 2015

Adv Funct Materials

Self Cite

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Previous studies indicate that immunostimulatory DNA‐based injectable hydrogels harboring unmethylated cytosine‐phosphate‐guanine (CpG) dinucleotides meet the requirements of an effective antigen delivery system, including safety, biodegradability, ease of administration, and stimulation of the innate immune system. However, rapid release of the model antigen ovalbumin (OVA) from the hydrogel limits its potential. Here, the aim is to achieve sustained OVA release from a DNA hydrogel through cationization of the antigen. Ethylenediamine (ED)‐conjugated cationized OVA (ED‐OVA), but not OVA, forms a complex with hexapod‐like structured DNA, a component of the DNA hydrogel. The release of ED‐OVA from the hydrogel is significantly slower than that of OVA. ED‐OVA mixed with CpG DNA hydrogel efficiently binds to mouse dendritic DC2.4 cells and results in high antigen presentation. Intratumoral injections of ED‐OVA/CpG DNA hydrogel significantly delays tumor growth of OVA‐expressing EG7‐OVA cells in mice. Then, a cationic OVA peptide antigen (R8‐L2‐pepI) consisting of an OVA MHC class I epitope, octaarginine, and a linker is designed. Intratumoral injections of R8‐L2‐pepI/CpG DNA hydrogel eradicate tumors in five out of six mice. Thus, it is concluded that a vaccine consisting of immunostimulatory CpG DNA hydrogel and cationized antigens can be effective for cancer immunotherapy.

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Increased immunostimulatory activity of polypod-like structured DNA by ligation of the terminal loop structures

Cited by 16 publications

References 27 publications

Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles

Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles

Synthetic Nanoparticles for Vaccines and Immunotherapy

Induction of Potent Antitumor Immunity by Sustained Release of Cationic Antigen from a DNA‐Based Hydrogel with Adjuvant Activity

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