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Modulating the Cellular Immune Response of Oligonucleotides by Brush Polymer‐Assisted Compaction
Author(s) -
Cao Xueyan,
Lu Xueguang,
Wang Dali,
Jia Fei,
Tan Xuyu,
Corley Michelle,
Chen Xiaoying,
Zhang Ke
Publication year - 2017
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201701432
Subject(s) - innate immune system , nucleic acid , immune system , oligonucleotide , context (archaeology) , dna , microbiology and biotechnology , pattern recognition receptor , stimulator of interferon genes , polyethylene glycol , biology , biochemistry , immunology , paleontology
Unwanted stimulation of the innate immune system by foreign nucleic acids has been one of the major barriers preventing bioactive sequences from reaching market. Foreign nucleic acids can be recognized by multiple pattern recognition receptors (PRRs), which trigger a signaling cascade to activate host defense systems, leading to a range of side effects. This study demonstrates that polyethylene glycol (PEG)‐modified DNA strands can greatly reduce the activation of the innate immune system, and the extent of reduction is dependent upon polymer architecture. Highly branched brushes with long PEG side chains achieve the best suppression by blocking PRR interactions via a local steric effect. Interestingly, the brush polymer creates little barrier toward DNA–DNA interaction. Quantification of inflammatory cytokines in both mRNA and protein levels as well as the extent of cellular uptake shows a direct correlation between steric congestion and reduction of cellular immune response. These results suggest that the brush architecture offers unique advantages for PEGylating oligonucleotides in the context of minimizing unwanted immune system activation.