This invention belongs to the interdisciplinary field of
pharmaceutical formulation and
gene therapy, and discloses a dsRNA targeting ALK7, its composition, and its applications. The ALK7-targeting dsRNA comprises a
sense strand and an antisense strand. The antisense strand includes a complementary region to the ALK7
RNA transcript, and the complementary region contains at least 15 consecutive nucleotides differing from one of the antisense sequences listed in Tables 1-2 by 0, 1, 2, or 3 nucleotides. The
nucleotide sequence of the
sense strand is as shown in any one of SEQ ID NO. 6-277, and the
nucleotide sequence of the antisense strand is as shown in any one of SEQ ID NO. 278-549. The dsRNA of this invention, through
chemical modification, optimizes its
ribose and
phosphate ester structures to exhibit resistance to
nuclease degradation and significantly reduces the
negative charge carried by the molecule, enhancing its ability to permeate
cell membranes. Furthermore, this invention can reduce
fat accumulation at its source, improve
insulin resistance, and reduce the risk of other metabolic diseases.