Chapter title |
TLR9-Targeted SiRNA Delivery In Vivo.
|
---|---|
Chapter number | 15 |
Book title |
SiRNA Delivery Methods
|
Published in |
Methods in molecular biology, January 2016
|
DOI | 10.1007/978-1-4939-3112-5_15 |
Pubmed ID | |
Book ISBNs |
978-1-4939-3111-8, 978-1-4939-3112-5
|
Authors |
Hossain, Dewan Md Sakib, Moreira, Dayson, Zhang, Qifang, Nechaev, Sergey, Swiderski, Piotr, Kortylewski, Marcin, Dewan Md Sakib Hossain, Dayson Moreira, Qifang Zhang, Sergey Nechaev, Piotr Swiderski, Marcin Kortylewski |
Abstract |
The SiRNA strategy is a potent and versatile method for modulating expression of any gene in various species for investigational or therapeutic purposes. Clinical translation of SiRNA-based approaches proved challenging, mainly due to the difficulty of targeted SiRNA delivery into cells of interest and the immunogenic side effects of oligonucleotide reagents. However, the intrinsic sensitivity of immune cells to nucleic acids can be utilized for the delivery of SiRNAs designed for the purpose of cancer immunotherapy. We have demonstrated that synthetic ligands for the intracellular receptor TLR9 can serve as targeting moiety for cell-specific delivery of SiRNAs. Chemically synthesized CpG-SiRNA conjugates are quickly internalized by TLR9-positive cells in the absence of transfection reagents, inducing target gene silencing. The CpG-SiRNA strategy allows for effective targeting of TLR9-positive cells in vivo after local or systemic administration of these oligonucleotides into mice. |
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