National Institute of Advanced Industrial Science and Technology

Otsuka Pharmaceutical Company, Limited

Napa Jenomics Co., Ltd.

Takanori Kubo

Hideki Ohba

Hidekazu Toyobuku

Hirotake Hayashi

Kazuo Sakurai

Atsushi Uno

Jusaku Minari

An object of the present invention is to provide novel double-stranded RNA having an RNA interference effect, in which the cellular uptake and the resistance to enzymatic degradation are improved, without reducing the RNA interference effect. The cellular uptake and the resistance to enzymatic degradation of a complex of a polysaccharide having a &#x3b2;-1,3-glucan skeleton and double-stranded RNA can be significantly improved while maintaining the RNA interference effect, by fulfilling the following conditions (i) to (iii): (i) the double-stranded RNA has a sense strand consisting of a base sequence complementary to a target sequence in a target gene and an antisense strand containing a base sequence complementary to the sense strand, and the double-stranded RNA can inhibit expression of the target gene; (ii) the double-stranded RNA has a single-stranded polydeoxyadenine bound directly or via a linker to the end of at least one of the sense strand and the antisense strand; and (iii) the polysaccharide and the single-stranded polydeoxyadenine form a complex.

Complex of polysaccharide and double-stranded RNA

An object of the present invention is to provide a novel double-stranded RNA that has high resistance to nuclease and cellular uptake efficiency and that can produce an excellent RNA interference effect. The present invention provides a double-stranded lipid-modified RNA comprising an antisense strand having a nucleotide sequence complementary to a target sequence in a target gene, and a sense strand having a nucleotide sequence complementary to the antisense strand, the double-stranded RNA being capable of suppressing the expression of the target gene, and the sense strand having a double-stranded lipid bound directly or via a linker to at least one of the first to sixth nucleotides from the 5' end.

Double-stranded lipid-modified RNA having high RNA interference effect

An object of the present invention is to provide a novel double-stranded RNA that has high nuclease resistance and high cellular uptake efficiency, and that is capable of producing an excellent RNA interference effect. The present invention provides a lipid-modified double-stranded RNA comprising a sense strand having a nucleotide sequence complementary to a target sequence, and an antisense strand having a nucleotide sequence complementary to the sense strand, the double-stranded RNA being capable of inhibiting the expression of the target gene, the sense strand having a lipid linked to at least one of the first to sixth nucleotides from the 5' end side directly or via a linker.

Lipid-modified double-stranded RNA having potent RNA interference effect

Growing community of inventors

Hiroshima, Japan

Takanori Kubo