National Institute of Advanced Industrial Science and Technology

Agency of Industrial Science and Technology

Otsuka Pharmaceutical Company, Limited

Napa Jenomics Co., Ltd.

Hideki Ohba

Imre Sallay

Seiji Yasuda

Takanori Kubo

Hidekazu Toyobuku

Tsuyoshi Sakaki

Masao Shibata

Hirotake Hayashi

Fumio Yagi

Sawako Moriwaki

Toshihisa Sumi

Toru Ikegami

Sung Soo Park

Kazuo Sakurai

Atsushi Uno

Jusaku Minari

Yoko Fuke

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

An efficient method for therapeutic treatment of a leukemic patient is disclosed in which the patient's body fluid under external circulation is brought into direct contact with an adsorbent material capable of adsorbing the leukemic cells in the body fluid specifically and selectively. The leukemic cell-adsorbent material, which is used by filling a column to form an adsorbent bed, is a conjugate of a lectin protein extracted from, e.g.,beans or soybeans coupled with a physiologically inert carrier material such as a polysaccharide in the form of beads or a superparamagnetic material in the form of iron oxide-based magnetic beads.

[object Object]

Disclosed is a method for growth inhibition of human leukemic cells or therapeutic treatment method of a leukemic patient by using a medicament of which the effective ingredient is a methylsulfinylalkyl isothiocyanate such as 4-(methylsulfinyl)butyl isothiocyanate and 6-(methylsulfinyl)hexyl isothiocyanate, which can be prepared by extraction from the tissues of certain plants and can induce apoptosis in human leukemic cells. This medicament compound is little growth-inhibitive against normal cells as compared with leukemic cells, so that a remarkable therapeutic effect can be expected.

Leukemic cell growth inhibiting method

An efficient method for therapeutic treatment of leukemia is provided in which a patient's body fluid during external circulation is brought into direct contact with an adsorbent material capable of specifically and selectively adsorbing leukemic cells in the body fluid. The leukemic cell-adsorbing material is a composite of a lectin protein coupled with a physiologically inert carrier material such as a galactan polysaccharide in the form of beads. The lectin protein may be obtained from a mushroom fungus such as or a leguminous seed such as from the jequirity bean plant. The lectin protein and carrier material can be bound by forming chemical linkages between amino groups in the lectin protein and functional groups in the carrier material, and unreacted functional groups of the carrier material may be blocked with an amino acid. A leukemic cell-adsorbing column may be formed by filling the leukemic cell-adsorbing material into a tubular body to form an adsorbent bed. The tubular body may have an inner diameter of from 10 to 20 mm and a height of from 50 to 200 mm.

Leukemic cell-adsorbing material containing lectin protein from Agrocybe cylindracea or jequirity plant seed

Disclosed is an economical method for the preparation of chondroitin sulfates A and C useful as an effective ingredient of medicaments from fish scales as a waste material discharged from fishery in large quantities. Fish scales are enzymatically decomposed in an aqueous medium in the presence of a protease to isolate the chondroitin sulfate compounds and by-product polypeptides followed by removal of the by-product polypeptides from the aqueous solution by a cation-exchange treatment and then the aqueous solution of the chondroitin sulfate compounds is subjected to fractional precipitation by the addition of ethyl alcohol as the precipitant.

Method for the preparation of chondroitin sulfate compounds

Disclosed is an efficient and economical method for the preparation of N-glycolyl neuraminic acid in a high purity from an inexpensive abundant source material. The method comprises dispersing body tissues of an echinodermatous marine animal Cucumaria echinata in an aqueous medium, preferably, using a dry powder of the tissues prepared in advance, in which the tissues are proteolytically decomposed to isolate N-glycolyl neuraminic acid in the form of an aqueous solution containing polypeptides as a by-product, followed by separation of N-glycolyl neuraminic acid from the aqueous solution by removing the polypeptides and purification of the compound in a process utilizing an ion-exchange treatments.

Growing community of inventors

Kitakyushu, Japan

Hideki Ohba