The application of siRNA to medical treatments is increasingly expected because the siRNA can knock down target mRNA specifically and effectively. However, the development of an effective delivery system is indispensable to apply the siRNA to medical treatments. In recent years, it has been clarified that a therapeutic effect of naked siRNA on age-related macular degeneration (CNV) through its intraocular administration under a clinical trial does not result from a sequence-specific gene knockdown effect induced by siRNA but results from a non-sequence-specific effect via recognition by Toll-like receptor-3 (TLR-3) on cell surface. It has been considered important to develop a carrier that is stable outside cells and is capable of accurately delivering siRNA into the cells in any of in vivo siRNA applications.
Poly(L-lysine) or polyethylene imine, which has been long known as a cationic polymer for forming a polyion complex (PIC) with DNA to introduce a gene into eukaryotic cells and expressing the gene, has a problem in that the compound does not exhibit very high gene expression efficiency or exhibits high toxicity on cells, for example. A wide variety of cationic polymers have been provided in order to solve such problem. For example, a poly(L-lysine) derivative in which a hydrophilic group (e.g., polyethylene glycol) and a hydrophobic group (e.g., palmitoyl) have been introduced via an ε-amino group of poly(L-lysine) forms a vesicle in the presence of cholesterol in an aqueous medium and the vesicle aggregates gene-containing plasmid DNA to form a stable complex (Patent Document 1). Further, a PIC formed of plasmid DNA with a copolymer derivative whose cation charge and disulfide crosslink density have been modulated by the thiolation of an ε-amino group of poly(L-lysine) in a poly(L-lysine)-poly(ethylene glycol) copolymer shows high stability in an extracellular medium and effectively releases the DNA in an intracellular compartment (Non Patent Document 1, some of the inventors of the present invention are coauthors of Non Patent Document 1). Further, the inventors of the present invention have confirmed, as part of such research, that, when poly(N—[N-(2-aminoethyl)-2-aminoethyl]aspartamide (PAsp (DET))) having an ethylenediamine structure in a side chain and a block copolymer including the PAsp (DET) as one block component of the block copolymer are produced, such polymers show low cytotoxicity and introduce plasmid DNA into cells with high efficiency to express a gene incorporated into the DNA efficiently (see Non Patent Document 2, Patent Document 2, and Patent Document 3).
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