Suzhou Ribo Life Science Company, Ltd.

Daiwu Kang

Hongyan Zhang

Shan Gao

Lina Kong

Gengrong Chen

Tao Liu

NUCLEIC ACID, COMPOSITION AND CONJUGATE CONTAINING NUCLEIC ACID, PREPARATION METHOD THEREFOR AND USE THEREOF

NUCLEIC ACID, PHARMACEUTICAL COMPOSITION, CONJUGATE, PREPARATION METHOD, AND USE

Provided are a siRNA for inhibiting the expression of an angiopoietin-like protein 3 (ANGPTL3) gene, and a pharmaceutical composition and a conjugate comprising the siRNA; wherein each nucleotide in the siRNA is independently a modified or unmodified nucleotide, and the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence A, the nucleotide sequence A having the same length as the nucleotide sequence as represented by SEQ ID NO:1 with no more than 3 nucleotide differences; the antisense strand comprises a nucleotide sequence B, the nucleotide sequence B having the same length as the nucleotide sequence as represented by SEQ ID NO:2 with no more than 3 nucleotide differences.

Nucleic acid, composition and conjugate comprising the same, preparation method and use thereof

The present disclosure provides a siRNA for inhibiting the expression of apolipoprotein C3 (ApoC3) gene, and a pharmaceutical composition and a conjugate comprising the siRNA; wherein each nucleotide in the siRNA is independently a modified nucleotide, and the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence A, the nucleotide sequence A having the same length as the nucleotide sequence as represented by SEQ ID NO:1 with no more than 3 nucleotide differences; the antisense strand comprises a nucleotide sequence B, the nucleotide sequence B having the same length as the nucleotide sequence as represented by SEQ ID NO:2 with no more than 3 nucleotide differences.

Nucleic acid, composition and conjugate containing same, preparation method, and use thereof

Provided are a siRNA for inhibiting the expression of hepatitis B virus gene, and a pharmaceutical composition and conjugate containing the siRNA. Each nucleotide in the siRNA is independently a modified nucleotide. The siRNA comprises a sense strand and an antisense strand. The sense strand of the siRNA comprises a nucleotide sequence 1 having the same length and no more than three nucleotides different from the nucleotide sequence shown in SEQ ID NO: 155, and the antisense strand of the siRNA comprises a nucleotide sequence 2 having the same length and no more than three nucleotides different from the nucleotide sequence shown in SEQ ID NO: 156.

Nucleic acid, composition and conjugate comprising the same, and preparation method and use thereof

Provided are an siRNA for inhibiting expression of a Hepatitis B virus gene, and a pharmaceutical composition and conjugate containing the siRNA. Each nucleotide in the siRNA is an independently modified or unmodified nucleotide; the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence A; the length of the nucleotide sequence A is the same as that of a nucleotide sequence as shown in SEQ ID NO: 1, and the number of the nucleotide differences is not more than three; the antisense strand comprises a nucleotide sequence B; and the length of the nucleotide sequence B is the same as that of a nucleotide sequence as shown in SEQ ID NO: 2, and number of nucleotide differences is not more than three.

Provided is a siRNA for inhibiting HBV gene expression, including a sense strand and an antisense strand. The sense strand includes a nucleotide sequence 1, and the antisense strand includes a nucleotide sequence 2; the nucleotide sequence 1 and the nucleotide sequence 2 are at least partially reversely complementary to form a double-stranded region; the nucleotide sequence 1 and the nucleotide sequence shown in SEQ ID NO: 1 are equal in length, and no more than 3 nucleotide differences are generated; the nucleotide sequence 2 and the nucleotide sequence shown in SEQ ID NO: 2 are equal in length, and no more than 3 nucleotide differences are generated; nucleotides of the 7th, 8th, and 9th bits of the nucleotide sequence 1 and the 2nd, 6th, 14th, and 16th of the nucleotide sequence 2 are fluoro-modified nucleotides. Also provided are a pharmaceutical composition and a conjugate containing the siRNA.

Nucleic acid, pharmaceutical composition and conjugate containing nucleic acid, and use thereof

An siRNA conjugate having a structure as represented by formula (1) for inhibiting hepatitis B vims gene expression, comprising siRNA and a conjugated group, wherein the sense strand of the siRNA comprises a nucleotide sequence 1, and the antisense strand comprises a nucleotide sequence 2; the nucleotide sequence 1 and the nucleotide sequence 2 are, at least in part, reversely complementary to form a double-stranded region; the nucleotide sequence 1 and SEQ ID NO: 1 are equal in length and differ by no more than three nucleotides; the nucleotide sequence 2 and SEQ ID NO: 2 are equal in length and differ by no more than three nucleotides. The siRNA conjugate can specifically target liver cells and effectively solve the problem of siRNA delivery in vivo, and shows excellent activity and low toxicity to inhibit HBV gene expression while maintaining high stability of siRNA.

SiRNA conjugate, preparation method therefor and use thereof

Provided is a modified double-stranded oligonucleotide, in which the sense strand comprises a nucleotide sequence 1, the anti-sense strand comprises a nucleotide sequence 2, the nucleotide sequences 1 and 2 are both 19 nucleotides in length, and in the direction from 5' end to 3&#x2032; end, nucleotides at positions 7, 8 and 9 of the nucleotide sequence 1 and nucleotides at positions 2, 6, 14 and 16 of the nucleotide sequence 2 are all fluoro-modified nucleotides, and each nucleotide at other positions is independently one of non-fluoro-modified nucleotides. Further provided are a pharmaceutical composition and a conjugate comprising the oligonucleotide, and pharmaceutical use thereof.

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Suzhou, China

Daiwu Kang