Two or more nucleic acid molecules connected by a linker

Abstract

Two or more nucleic acid molecules are connected by a linker, such as a compound of formula I or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof.

Description

The present invention claims the priority to Chinese Patent Application No. CN202410109201.9 filed on January 25, 2024 and Chinese Patent Application No. CN202410707952.0 filed on May 31, 2024, which are incorporated herein by reference in their entirety as part of the disclosure of the present invention. FIELD OF THE INVENTION The present invention relates to the technical field of medical and pharmaceutical science, and particularly relates to two or more double-stranded RNAs connected by a linker, such as a compound of formula I or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof. BACKGROUND ART RNA interference is a phenomenon of specific and highly efficient degradation of the target mRNA induced by a double-stranded RNA (dsRNA, also known as siRNA). The use of a linker to connect two or more dsRNAs (including siRNA) for delivery enables multiple genes to be targeted at once, producing a synergistic effect. There is still a need in the art to develop more linkers for more efficient simultaneous delivery of two or more dsRNAs. SUMMARY OF THE INVENTION The present invention relates to a compound of formula I or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof: Gi Si X S2 G2 q wherein each group is defined as follows. The present invention further relates to a cell comprising a compound as described above. The present invention further relates to a pharmaceutical composition comprising a compound as described above, or a cell as described above, and optionally a pharmaceutically acceptable carrier or excipient. The present invention further relates to a kit comprising a compound as described above, or a cell as described above. The present invention further relates to the use of a compound of the present invention for the manufacture of a medicament for treating and / or preventing diseases. DETAILED DESCRIPTION OF THE INVENTION Definitions Chemical Definitions Definitions of specific functional groups and chemical terms are described in more detail as follows. When a numerical range is provided, it is intended that a particular numerical point and sub-range within said range be included. For example, "Ci-6 alkyl" includes alkyls Ci, C2, C3, C4, C5, Ce, C1-6, C1-5, C1-4, C1-3, C1-2, C2-6, C2-5, C2-4, C2-3, C3-6, C3-5, C3-4, C4-6, C4-5, and C5-6. "C1-6 alkyl" refers to any straight-chain or branched hydrocarbon group being saturated and with 1 to 6 carbon atoms. In some embodiments, C1-4 alkyl is preferred. Examples of C1-6 alkyl described herein include: methyl (Ci), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), isobutyl (C4), n-pentyl (C5), 3-pentyl (C5), pentyl (C5), neopentyl (C5), 3-methyl-2-butyl (C5), tert-pentyl (C5) and n-hexyl (Ce). The term "C1-6 alkyl" also includes any heteroalkyl in which one or more (e.g., 1, 2, 3, or 4) carbon atoms are replaced with heteroatoms (e.g., oxygen, sulfur, nitrogen, boron, silicon, phosphorus). The alkyls may be optionally substituted by one or more substituents, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. The conventional abbreviations for alkyl include: Me(-CH3), Et(-CH2CH3), iPr(-CH(CH3)2), nPr(-CH2CH2CH3), n-Bu(-CH2CH2CH2CH3), or i-Bu(-CH2CH(CH3)2). "C2-6 alkenyl" refers to a straight-chain or branched hydrocarbon group with 2 to 6 carbon atoms and at least one carbon-carbon double bond. In some embodiments, C2-4 alkenyl is preferred. Examples of C2-6 alkenyl include, but are not limited to: vinyl (C2), 1-propenyl (C3), 2-propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), pentenyl (C5), pentadienyl (C5), and hexenyl (Ce). The term "C2-6 alkenyl" also includes any heteroalkenyl in which one or more (e.g., 1, 2, 3, or 4) carbon atoms are replaced with heteroatoms (e.g., oxygen, sulfur, nitrogen, boron, silicon, phosphorus). The alkenyls may be optionally substituted by one or more substituents, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. "C2-6 alkynyl" refers to a straight-chain or branched hydrocarbon group with 2 to 6 carbon atoms and at least one carbon-carbon triple bond and optionally one or more carbon-carbon double bonds. In some embodiments, C2-4 alkynyl is preferred. Examples of C2-6 alkynyl include, but are not limited to: ethynyl (C2), 1-propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), 2-butynyl (C4), pentynyl (C5), and hexynyl (Ce). The term "C2-6 alkynyl" also includes any heteroalkynyl in which one or more (e.g., 1,2,3, or 4) carbon atoms are replaced with heteroatoms (e.g., oxygen, sulfur, nitrogen, boron, silicon, phosphorus). The alkynyls may be optionally substituted by one or more substituents, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. "Halogenated" or "halogen" refers to (substitution by) fluorine (F), chlorine (Cl), bromine (Br), and iodine (I). Accordingly, "C1-6 haloalkyl" refers to the aforementioned "C1-6 alkyl", with one or more halogen groups. In some embodiments, a C1-4 haloalkyl is particularly preferred, and a C1-2 haloalkyl is even more preferred. Exemplary haloalkyls include, but are not limited to: -CF3, -CH2F, -CHF2, -CHFCH2F, -CH2CHF2, -CF2CF3, -CCI3, -CH2CI, -CHQ2, and 2,2,2-trifluoro-l,l-dimethyl-ethyl. The haloalkyls may be substituted at any substitutable connection site, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. "C3-10 cycloalkyl" refers to a non-aromatic cyclic hydrocarbon group with 3 to 10 ring carbon atoms and no heteroatoms. In some embodiments, C4-7 cycloalkyl and C3-6 cycloalkyl are particularly preferred, and C5-6 cycloalkyl is even more preferred. A cycloalkyl herein also includes a ring system in which an aforementioned cycloalkyl ring is fused with one or more aryls or heteroaryls through any connection site(s) on the cycloalkyl ring; in this context, the number of carbons still represents the number of carbons in the cycloalkyl system. Examples of said cycloalkyls include, but are not limited to: cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), and cycloheptatrienyl (C7). The cycloalkyls may be optionally substituted by one or more substituents, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. The term herein "3-membered to 10-membered heterocyclyl" refers to a group of a 3-membered to 10membered non-aromatic ring system with ring carbon atom(s) and 1 to 5 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus and silicon. In said heterocyclyl containing one or more nitrogen atoms, the connection site may be a carbon or nitrogen atom as long as the valence permits. In some embodiments, a 4-membered to 10-membered heterocyclyl is preferred, which is a 4-membered to 10-membered non-aromatic ring system with ring carbon atom(s) and 1 to 5 ring heteroatoms; In some embodiments, a 3-membered to 8-membered heterocyclyl is preferred, which is a 3-membered to 8-membered nonaromatic ring system with ring carbon atom(s) and 1 to 4 ring heteroatoms; preferably a 3-membered to 6-membered heterocyclyl as a 3-membered to 6-membered non-aromatic ring system with ring carbon atom(s) and 1 to 3 ring heteroatoms; preferably a 4-membered to 7-membered heterocyclyl as a 4-membered to 7-membered non-aromatic ring system with ring carbon atom(s) and 1 to 3 ring heteroatoms; more preferably a 5-membered to 6-membered heterocyclyl as a 5-membered to 6-membered non-aromatic ring system with ring carbon atom(s) and 1 to 3 ring heteroatoms. A heterocyclyl herein also includes a ring system in which an aforementioned heterocyclyl ring is fused with one or more cycloalkyls through any connection site(s) on the cycloalkyl ring, or said heterocyclyl includes a ring system in which an aforementioned heterocyclyl ring is fused with one or more aryls or heteroaryls through any connection site(s) on the heterocyclyl ring; in these contexts, the number of ring members still represents the number of ring members in the heterocyclyl ring system. Exemplary 3-membered heterocyclyls containing one heteroatom include, but are not limited to: aziridinyl, oxiranyl, and thiorenyl. Exemplary 4membered heterocyclyls containing one heteroatom include, but are not limited to: azetidinyl, oxetidinyl, and thietanyl. Exemplary 5-membered heterocyclyls containing one heteroatom include, but are not limited to: tetrahydrofuryl, dihydrofuryl, tetrahydrothienyl, dihydrothienyl, pyrrolidinyl, dihydropyrrolyl, and pyrroli-2,5-dione. Exemplary 5-membered heterocyclyls containing two heteroatoms include, but are not limited to: dioxolanyl, oxasulfuranyl, disulfuranyl, and oxazolidin-2-one. Exemplary 5-membered heterocyclyls containing three heteroatoms include, but are not limited to: triazolinyl, oxadiazolinyl and thiadiazolinyl. Exemplary 6-membered heterocyclyls containing one heteroatom include, but are not limited to: piperidinyl, tetrahydropyranyl, dihydropyridyl and thianyl. Exemplary 6-membered heterocyclyls containing two heteroatoms include, but are not limited to: piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6-membered heterocyclyls containing three heteroatoms include, but are not limited to: triazinanyl. Exemplary 7-membered heterocyclyls containing one heteroatom include, but are not limited to: azepanyl, oxepanyl, and thiepanyl. Exemplary 5-membered heterocyclyls each of which is fused with a C6 aryl ring (also referred to herein as a 5,6-bicycloheterocyclyl) include, but are not limited to: dihydroindolyl, isodihydroindolyl, dihydrobenzofuryl, dihydrobenzothienyl, and benzoxazolinonyl. Exemplary 6-membered heterocyclyls each of which is fused with a C6 aryl ring (also referred to herein as a 6,6-bicycloheterocyclyl) include, but are not limited to: tetrahydroquinolinyl, and tetrahydroisoquinolinyl. The heterocyclyls may be optionally substituted by one or more substituents, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. "Ce-io aryl” refers to a monocyclic or polycyclic (e.g., bicyclic) group that is a 4n+2 aromatic ring system having 6 to 10 ring carbon atoms and no heteroatom (e.g., with 6 or 10 it electrons shared in a cyclic arrangement). In some embodiments, an aryl has six ring carbon atoms (“C6 aryl”; e.g., phenyl). In some embodiments, an aryl has ten ring carbon atoms (“CIO aryl”; e.g., a naphthyl, such as 1-naphthyl and 2-naphthyl). An aryl herein also includes a ring system in which an aforementioned aryl ring is fused with one or more cycloalkyls or heterocyclyls through the connection sites on said aryl ring; in this context, the number of carbon atoms still represents the number of carbon atoms in said aryl ring system. The aryls may be optionally substituted by one or more substituents, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. "5-membered tol4-membered heteroaryl" refers to a 5-membered to 14-membered monocyclic or bicyclic group of a 4n+2 aromatic ring system (e.g., with 6, 10 or 14 it electrons shared in a cyclic arrangement) that has ring carbon atom(s) and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen and sulfur. In said heteroaryl containing one or more nitrogen atoms, the connection site may be a carbon or nitrogen atom as long as the valence permits. A bicyclic heteroaryl system herein may comprise one or more heteroatoms in one or both rings thereof. A heteroaryl herein also includes a ring system in which an aforementioned heteroaryl ring is fused with one or more cycloalkyls or heterocyclyls through the connection sites on said heteroaryl ring; in this context, the number of carbon atoms still represents the number of carbon atoms in said heteroaryl ring system. In some embodiments, a 5-membered to 10-membered heteroaryl is preferred, which is a 4n+2 aromatic ring system of a 5-membered to 10-membered monocyclic or bicyclic ring with ring carbon atom(s) and 1 to 4 ring heteroatoms. In some other embodiments, a 5-membered to 6-membered heteroaryl is particularly preferred, which is a 4n+2 aromatic ring system of a 5-membered to 6-membered monocyclic or bicyclic ring with ring carbon atom(s) and 1 to 4 ring heteroatoms. Exemplary 5-membered heteroaryls containing one heteroatom include, but are not limited to: pyrrolyl, furyl, and thienyl. Exemplary 5-membered heteroaryls containing two heteroatoms include, but are not limited to: imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryls containing three heteroatoms include, but are not limited to: triazolyl, oxadiazolyl (e.g., 1,2,4-oxadiazolyl), and thiadiazolyl. Exemplary 5-membered heteroaryls containing four heteroatoms include, but are not limited to: tetrazolyl. Exemplary 6-membered heteroaryls containing one heteroatom include, but are not limited to: pyridinyl. Exemplary 6-membered heteroaryls containing two heteroatoms include, but are not limited to: pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryls containing three or four heteroatoms include, but are not limited to: triazinyl, and tetrazinyl. Exemplary 7-membered heteroaryls containing one heteroatom include, but are not limited to: azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6-bicycloheteroaryls include, but are not limited to: indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothienyl, isobenzothienyl, benzofuryl, benzoisofuryl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzooxadiazolyl, benzothiazolyl, benzoisothiazolyl, benzothiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6-bicycloheteroaryls include, but are not limited to: naphthalidinyl, pteridinyl, quinolyl, isoquinolyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. The heteroaryls may be optionally substituted by one or more substituents, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. Alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl as defined herein are optionally substituted groups. Exemplary substituents on carbon atoms include, but are not limited to: halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR33, -ON(Rbb)2, -N(Rbb)2, -N(Rbb)3+X-, -N(0Rcc)Rbb, -SH, -SRaa, -SSRCC, -C(=O)Raa, -CO2H, -CHO, -C(ORcc)2, -CO2R33, -OC(=O)Raa, -OCO2Raa, -C(=O)N(Rbb)2, -OC(=O)N(Rbb)2, -NRbbC(=O)Raa, -NRbbCO2Raa, -NRbbC(=O)N(Rbb)2, -C(=NRbb)Raa, -C(=NRbb)ORaa, -OC(=NRbb)Raa, -OC(=NRbb)ORaa, -C(=NRbb)N(Rbb)2, -OC(=NRbb)N(Rbb)2, -NRbbC(=NRbb)N(Rbb)2, -C(=O)NRbbSO2Raa, -NRbbSO2Raa, -SO2N(Rbb)2, -SO2Raa, -SO2ORaa, -OSO2Raa, -S(=O)Raa, -OS(=O)Raa, -Si(Raa)3, -OSi(Raa)3, -C(=S)N(Rbb)2, -C(=O)SRaa, -C(=S)SRaa, -SC(=S)SRaa, -SC(=O)SRaa, -OC(=O)SRaa, -SC(=O)ORaa, -SC(=O)Raa, -P(=O)2Raa, -OP(=O)2Raa, -P(=O)(Raa)2, -OP(=O)(Raa)2, -OP(=O)(ORcc)2, -P(=O)2N(Rbb)2, -OP(=O)2N(Rbb)2, -P(=O)(NRbb)2, -OP(=O)(NRbb)2, -NRbbP(=O)(ORcc)2, -NRbbP(=O)(NRbb)2, -P(Rcc)2, -P(Rcc)3, -OP(Rcc)2, -OP(Rcc)3, -B(Raa)2, -B(ORCC)2, -BRaa(ORcc), alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 Rdd groups; or wherein two geminal hydrogens at a carbon atom are substituted by a group, such as =0, =S, =NN(Rbb)2, =NNRbbC(=0)Raa, =NNRbbC(=0)0Raa, =NNRbbS(=O)2Raa, =NRbb, or =NORCC; wherein each of Raa is independently selected from alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, or two Raa groups are connected each other to form a heterocyclyl ring or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 Rdd groups; each of Rbb is independently selected from: hydrogen, -OH, -OR33, -N(RCC)2, -CN, -C(=O)R33, -C(=O)N(RCC)2, -CO2R33, -SO2R33, -C(=NRcc)ORaa, -C(=NRcc)N(Rcc)2, -SO2N(Rcc)2, -SO2Rcc, -SO2ORcc, -SOR33, -C(=S)N(Rcc)2, -C(=O)SRCC, -C(=S)SRCC, -P(=O)2R33, -P(=O)(R33)2, -P(=O)2N(Rcc)2, -P(=O)(NRcc)2, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, or two Rbb groups are connected each other to form a heterocyclyl ring or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl group is independently substituted with 0, 1, 2, 3, 4 or 5 Rdd groups; wherein each of Rcc is independently selected from hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, or two Rcc groups are connected to form a heterocyclyl ring or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 Rdd groups; each of Rdd is independently selected from: halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -ORee, -0N(Rff)2, -N / R^z, -N / R^s+X; -N(0Ree)Rff, -SH, -SRee, -SSRee, -C(=O)Ree, -CO2H, -CO2Ree, -OC(=O)Ree, -OCO2Ree, -C(=O)N(Rff)2, -OC(=O)N(Rff)2, -NRffC(=O)Ree, -NRffCO2Ree, -NRffC(=0)N(Rff)2, -C(=NRff)ORee, -OC(=NRff)Ree, -OC(=NRfi)ORee, -C(=NRfi)N(Rfi)2, -0C(=NRfi)N(Rfi)2, -NRffC(=NRfi)N(Rfi)2, -NRffSO2Ree, -SO2N(Rrrh. -SO2Ree, -SO2ORee, -OSO2Ree, -S(=O)Ree, -Si(Ree)3, -OSi(Ree)3, -C(=S)N(Rff)2, -C(=O)SRee, -C(=S)SRee, -SC(=S)SRee, -P(=O)2Ree, -P(=O)(Ree)2, -OP(=O)(Ree)2, -OP(=O)(ORee)2, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 Rgg groups, or two geminal Rdd substituents may be combined to form =0 or =S; each of Ree is independently selected from: alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl and heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 Rgg groups; wherein each of Rff is independently selected from hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, or two Rff groups are connected each other to form a heterocyclyl ring or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 Rgg groups; each of Rgg is independently selected from: halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OCi-eAlkyl, -ON(Ci-6Alkyl)2, -N(Ci-6Alkyl)2, -N(Ci-6Alkyl)3+X-, -NH(Ci-6Alkyl)2+X-, -NH2(Ci-6Alkyl)+X-, -NH3+X-, -N(OCi-6Alkyl)(Ci-6Alkyl), -N(OH)(Ci-6Alkyl), -NH(OH), -SH, -SCi-6Alkyl, -SS(Ci-6Alkyl), -C(=O)(Ci-6Alkyl), -CO2H, -CO2(Ci-6Alkyl), -OC(=O)(Ci-6Alkyl), -OCO2(Ci-6Alkyl), -C(=O)NH2, -C(=O)N(Ci-6Alkyl)2, -OC(=O)NH(Ci-6Alkyl), -NHC(=O)(Ci-6Alkyl), -N(Ci-6Alkyl)C(=O)(Ci-6Alkyl), -NHCO2(Ci-6Alkyl), -NHC(=O)N(Ci-6Alkyl)2, -NHC(=O)NH(Ci-6Alkyl), -NHC(=O)NH2, -C(=NH)O(Ci-6Alkyl), -OC(=NH)(Ci-6Alkyl), -OC(=NH)OCi-6Alkyl, -C(=NH)N(Ci-6Alkyl)2, -C(=NH)NH(Ci-6Alkyl), -C(=NH)NH2, -OC(=NH)N(Ci-6Alkyl)2, -OC(NH)NH(Ci-6Alkyl), -OC(NH)NH2, -NHC(NH)N(Ci-6Alkyl)2, -NHC(=NH)NH2, -NHSO2(Ci-6Alkyl), -SO2N(Ci-6Alkyl)2, -SO2NH(Ci-6Alkyl), -SO2NH2, -SO2Ci-6Alkyl, -SO2OCi-6Alkyl, -OSO2Ci-6Alkyl, -SOCi-6Alkyl, -Si(Ci-6Alkyl)3, -OSi(Ci-6Alkyl)3, -C(=S)N(Ci-6Alkyl)2, C(=S)NH(Ci-6Alkyl), C(=S)NH2, -C(=O)S(Ci-6Alkyl), -C(=S)SCi-6Alkyl, -SC(=S)SCi-6Alkyl, -P(=O)2(Ci-6Alkyl), -P(=O)(Ci-6Alkyl)2, -OP(=O)(Ci-6Alkyl)2, -OP(=O)(OCi-6Alkyl)2, Ci-Alkyl. Ci-eHaloalkyl, C2-CeAlkenyl, C2-CeAlkynyl, Cs-CvCycloalkyl, Ce-CioAryl, C’,-C-Hctcrocyclyl. C5-CioHeteroaryl; or two geminal Rgg substituents may be connected to form =0 or =S; wherein, X- is a counterion. Exemplary substituents on a nitrogen atom include, but are not limited to: hydrogen, -OH, -ORaa, -N(RCC)2, -CN, -C(=O)Raa, -C(=O)N(Rcc)2, -CO2Raa, -SO2Raa, -C(=NRbb)Raa, -C(=NRcc)ORaa, -C(=NRCC)N(RCC)2, -SO2N(RCC)2, -SO2Rcc, -SO2ORcc, -SORaa, -C(=S)N(Rcc)2, -C(=O)SRcc, -C(=S)SRcc, -P(=O)2Raa, -P(=O)(Raa)2, -P(=O)2N(RCC)2, -P(=O)(NRcc)2, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, or two Rcc groups connecting to said nitrogen atom are connected to form a heterocyclyl ring or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 Rdd groups, and wherein Raa, Rbb, Rcc and Rdd are as described above. When any variable (e.g., R) occurs more than once in the composition or structure of a compound, the definition of the variable is independent for each occurrence. Thus, for example, if a group is substituted with 0 to 2 R, the group may optionally be substituted with up to two R, wherein the definition of R is independent for each occurrence. Furthermore, combinations of substituents and / or variants thereof are permissible only if such combinations result in stable compounds. When one of the variables is a single bond, it means that the two groups linked by the single bond are connected directly. For example, when L in A-L-B represents a single bond, the structure of A-L-B is actually A-B. When an enumerated linking group (i.e., divalent group) does not indicate its linking direction, the linking direction is arbitrary. For example, when the linking group L in A-L-B is -M-W-, -M-W- can be linked to variables A and B in the same direction in the reading order from left to right to form A-MW-B, or it can be linked to rings A and B in the reverse direction in the reading order from left to right to form A-WM-B. Some additional definitions The term "nucleic acid molecule" as used herein refers to its meaning as is generally accepted in the art. A nucleic acid molecule generally refers to a molecule consisting of nucleotides, including but not limited to siRNA, ASO, and shRNA. The term "nucleotide" as used herein refers to its meaning as is generally accepted in the art. A nucleotide generally comprises a heterocyclic base moiety (i.e., a base), a sugar moiety, and an intemucleoside linkage (e.g., a phosphate group or a phosphorothioate group). The base can be a natural base (A, U, T, C, G, collectively referred to herein as N), a modified base, or a base analog. Additionally, the nucleotides can be unmodified or modified at the sugar, intemucleoside linkage, or base moiety (also referred to interchangeably as nucleotide analogs, nonnatural nucleotides, non-standard nucleotides, and the like). A naturally occurring intemucleoside linkage refers to a 3' to 5' phosphodiester linkage (also referred to herein as a 3'-5' phosphodiester linkage). Modified nucleotides include inverted nucleotides connected to the front and back nucleotides via a 5' to 5' phosphodiester linkage and a 3' to 3' phosphodiester linkage. The term "2'-5' ribonucleotide" as used herein refers to its meaning as is generally accepted in the art. In contrast to a native ribonucleotide (i.e., 3'-5' ribonucleotide), the phosphate is attached at the 2' position rather than at the 3' position of the sugar moiety, including but not limited to A2p, C2p, G2p, and U2p, wherein A2p is adenosine 2'- phosphate, C2p is cytidine 2'-phosphate, G2p is guanosine 2'-phosphate, and U2p is uridine 2'-phosphate. The term "2'-5' deoxyribonucleotide" as used herein refers to its meaning as is generally accepted in the art. In contrast to a native deoxyribonucleotide (i.e., 3'-5' deoxyribonucleotide), the phosphate is attached at the 2' position rather than at the 3' position of the sugar moiety. The term "abasic" as used herein refers to its meaning as is generally accepted in the art. For nucleotides, the term generally refers to a sugar moiety (1) lacking a base, or (2) having a hydrogen atom or other non-base chemical groups in place of a base at the T position of the sugar moiety. In one embodiment, a compound of the present invention may contain one or more abasic moieties that are ribose, deoxyribose, or dideoxyribose. The term "sugar moiety" as used herein refers to a natural or modified sugar ring or sugar surrogate. As used herein, galactose is OH OH H0\Cq HO- Ci-6 alkylene-OH, KO e.g. oh T HN. ..0¾ OH HO < HdC^OH , galactosamine is NH2 , which is optionally substituted with -Ac, -C(0)- •OH HN_ O  '—\ oh ; A-acetylgalactosamine is HO,. ), glucose is ( HO y—o. OH 2>             Hi =—r oh          . oh ), mannose is OK OH HO / HO^S^OH nhac , N-acetylglucosamine is I .n                  <oh > 1           •       •. • OH > , glucuronic acid is OH .OH neuraminic acid (sialic acid) is OH Z-?-VzoH hooh OH , xylose i\OH 6hSL_ is 0-. ">-'"OH OH , or fucose is The term "blunt end" as used herein refers to that there are no unpaired nucleotides at that end of the dsRNA, i.e., there are no nucleotide overhangs at that end. A "blunt-ended RNA" is an RNA that is double-stranded throughout its length, i.e., there are no nucleotide overhangs at either end of the molecule. The term "overhang" as used herein refers to at least one unpaired nucleotide that protrudes from the doublestranded region of a dsRNA. Nucleotide overhangs exist, for example, when the 3'-end of one strand of the dsRNA extends beyond the 5'-end of the other strand, or vice versa. A dsRNA can comprise an overhang of at least one nucleotide, at least two nucleotides, at least three nucleotides, at least four nucleotides, at least five nucleotides, or more. A nucleotide overhang may comprise or consist of a nucleotide / modified nucleotide (including a deoxynucleotide / nucleoside). One or more overhangs can be on the sense strand, the antisense strand, or any combination thereof. The overhang having one or more nucleotides may be present at the 5'-end, 3'-end, or both ends of the antisense or sense strand of the dsRNA. The term " terminal modification" as used herein refers to a modification at an end (i.e., the 5' end and / or the 3' end) of a nucleic acid strand, including but not limited to optionally substituted abasic nucleotides, inverted nucleotides, 'o O’ H 0^ and compounds in PCT Publication No, WO2024002006A1 below. No. Structural Formula STM1 / o _o ' / o STM2a and STM2b O— 9—0 y— o-         o A— o \ y—_O STM3 "o STM4 A} d STM5a and STM5b 1                                              L and        / ° STM6a and STM6b O 1 \ J- O o % T3 S 1' o \ STM7a and STM7b / and        - STM8a and STM8b XN^           XN^ ___ /     X___y   4s         y and        / ° STM9a and STM9b 0   0 /      *                 J1 ,             ,0 and         / STM 10a and STM 10b nC3° nCZ^° cr                 0 * \T y -°     and       / ° STMllaand STMllb \ o °—r \ z-- 1 ° Z S & o o—I \ z-" 1 ° Z STM 12 STM 13 o x° STM 14a and STM 14b j      ,0 and / STM 15a and STM 15b XN"         XN-" ,       ,0 and In the above table, "*" represents a chiral center selected from the (S) or (R) absolute configuration, or the racemic form thereof. The substituted terminal modifications may include terminal modifications conjugated to the GalNAc molecule in a manner known in the art. Representative structures are, for example, (GL35), and o x (GL36). The term "IB" as used herein refers to an inverted abasic deoxyribonucleotide, which is an abasic nucleotide and can be of the following three structures depending on its position / connection method in dsRNA. IB is well known in the art. See, for example, F. Czaudema, Nucleic Acids Res., 2003, 31(11), 2705-16 and PCT Publication Nos. WO2016011123 and WO2019051402. The term "STM1" as used herein refers to a molecule of the following structure as described in PCT Publication No. WO2024002006A1. The term "siRNA" herein is a class of dsRNA molecules each of which can mediate the silencing of target 15 RNA (e.g., mRNA, e.g., transcript of a gene encoding a protein) complementary thereto. A siRNAs is generally 8 double-stranded, including an antisense strand complementary to the target RNA thereof and a sense strand complementary to this antisense strand. For the sake of convenience, such an mRNA is also referred to herein as mRNA to be silenced. And such a gene is also called target gene. Usually, an RNA to be silenced herein is an endogenous gene or a pathogen gene. In addition, RNAs other than mRNA (e.g., tRNA) as well as viral RNA may also be targeted. The term "antisense strand" herein refers to a strand of a siRNA, wherein said strand contains a region that is completely, sufficiently or substantially complementary to the target sequence thereof. The term "sense strand" herein refers to a strand of a siRNA, wherein said strand contains a region that is completely, sufficiently or substantially complementary to a region of an antisense strand as defined herein. The term "complementary region" herein refers to a region on an antisense strand that is completely, sufficiently or substantially complementary to the target mRNA sequence thereof. In cases where a complementary region is incompletely complementary to the target sequence thereof, a mismatch may be located in an internal or terminal region of the molecule. Typically, a mismatch most tolerant is located in a terminal region, e.g., within 5, 4, 3, 2 or 1 nucleotide at the 5' and / or 3' end. A region in an antisense strand, which is most sensitive to mismatch, is called "seed region". For example, in a siRNA containing a strand of 19 nt, the 19th site (counting from the 5' end to the 3' end) can tolerate some mismatches. The term "complementary" refers to the ability of a first polynucleotide to hybridize with a second polynucleotide under certain conditions, such as stringent conditions. For example, stringent conditions may include 400 mM NaCl, 40 mM PIPES pH 6.4, 1 mM EDTA, and 50°C or 70°C for 12-16 horns. With respect to fulfilling the above required capabilities related to the hybridization ability thereof, said "complementary" sequences may also include or be entirely composed of non-Watson-Crick base pairs and / or base pairs formed from non-natural as well as modified nucleotides. Such non-Watson-Crick base pairs include, but are not limited to, G:U wobble base pairing or Hoogsteen base pairing. A polynucleotide that is "at least partially complementary", "sufficiently complementary" or "substantially complementary" to a messenger RNA (mRNA) refers to a polynucleotide that is substantially complementary to a continuous portion of the mRNA of interest. For example, a polynucleotide is at least partially complementary to an mRNA encoding PCSK9, when the sequence thereof is substantially complementary to an uninterrupted portion of said PCSK9 mRNA. The terms "complementary," "completely complementary," "sufficiently complementary" and "substantially complementary" as used herein may be applied to base pairing between the sense strand and antisense strand of a siRNA, or between the antisense strand of a siRNA reagent and the target sequence thereof. "Sufficiently complementary" refers to the extent to which the sense strand only needs to be complementary to the antisense strand to maintain the overall double-stranded character of the molecule. In other words, although perfect complementarity is generally desired, in some cases, particularly in the antisense strand, one or more, e.g., 6, 5, 4, 3, 2, or 1 mismatch (relative to the target mRNA) may be included, but the sense and antisense strands can still maintain the overall double-stranded character of the molecule. The term "shRNA" herein refers to short hairpin RNA. An shRNA comprises two short inverted repeat sequences. An shRNA cloned into an shRNA expression vector comprises two short inverted repeat sequences, separated by a loop sequence, forming a hairpin structure and controlled by the RNA polymerase III (pol III) promoter. Subsequently, 5 to 6 Ts are ligated as transcription terminators of pol III. "Nucleoside" is a compound comprising two substances: one is a purine base or a pyrimidine base, and the other is a ribose or a deoxyribose; "nucleotide" is a compound comprising three substances: one is a purine base or a pyrimidine base, another is a ribose or deoxyribose, and the third is a phosphoric acid; and "oligonucleotide" refers to, for example, a nucleic acid molecule (RNA or DNA) with a length of less than 100, 200, 300 or 400 nucleotides. The term "base" is a fundamental building block of nucleosides, nucleotides and nucleic acids; as always containing nitrogen, said base is also referred to as "nitrogenous base." Unless otherwise specified, the capital letters herein, i.e., A, U, T, G and C, denote the bases of nucleotides, which is adenine, uracil, thymine, guanine and cytosine, respectively. As used herein, the "modification" of nucleotides includes, but is not limited to: methoxyl substitution (methoxy-modified), fluorine substitution (fluoro-modified), connection with a phosphorothioate group, or protection with a conventional protecting group. For example, a fluoro-modified nucleotide refers to a nucleotide formed by substituting the hydroxyl at the 2' position of the ribosyl of the nucleotide with a fluorine atom, while a methoxy-modified nucleotide refers to a nucleotide formed by substituting the 2'-hydroxyl of the ribosyl with a methoxyl. "Modified nucleotides" herein include, but are not limited to: a 2'-O-methyl modified nucleotide, a 2'-fluoro modified nucleotide, a 2'-deoxy-modified nucleotide, an inosine ribonucleotide, an abasic nucleotide, an inverted abasic deoxyribonucleotide, a nucleotide comprising a phosphorothioate group, a nucleotide modified by vinylphosphonate, a locked nucleotide, 2'-amino-modified nucleotide, 2'-alkyl-modified nucleotide, a morpholino nucleotide, a phosphoramidate, a non-natural base comprising nucleotide, and a terminal nucleotide linked to a cholesteryl derivative or a dodecanoic acid bisdecylamide group, deoxyribonucleotide, or a nucleotide with protection of a conventional protecting group. For example, a 2'-fluoro modified nucleotide refers to a nucleotide formed by substituting the hydroxyl at the 2' position of the ribosyl in a nucleotide with a fluorine atom. Said 2'-deoxy-modified nucleotide refers to a nucleotide formed by substituting the 2'-hydroxyl of the ribosyl with a methoxyl. The term "SCP modification" as used herein refers to a modified nucleotide of the following structure: o nn^J!            Base HO          f O °\ , wherein Base is independently selected from H, a modified or unmodified base, or a leaving group. Preferably, Base is an unmodified base, including an adenine base, a guanine base, a uracil base, and a cytosine base. In other embodiments, Base is a modified base. The SCP modifications can be found, for example, in PCT Publication No. WO2023241587A1. The term "phosphorothioate intemucleotide linkage" as used herein refers to a modification in which two adjacent left and right nucleotides are linked by a phosphorothioate group. The term “ligand moiety” as used herein refers to a chemical component conjugated with a siRNA, wherein the moiety is capable of changing the distribution, targeting, or lifespan of the siRNA. In a preferred embodiment, such a ligand offers enhanced affinity for selected targets, such as molecules, cells or cell types, and compartments (e.g., cellular or organ compartments, tissues, organs, or regions of the body), compared to for example a siRNA without such a ligand. Exemplary ligand moieties are, for example, ligands comprising GalNAc, ligands comprising an aliphatic chain, and ligands designed based on a small molecule compound. The term "amino acid residue" refers to any natural or synthetic amino acid residue, which is not limited to those in the group consisting of 20 naturally occurring amino acids, wherein the residue refers to the remaining portion of an amino acid connected by a peptide bond after dehydration. The 20 naturally occurring amino acid residues are selected from the group consisting of: alanine (Ala or A), cysteine (Cys or C), aspartic acid (Asp or D), glutamic acid (Glu or E), phenylalanine (Phe or F), glycine (Gly or G), histidine (His or H), isoleucine (He or I), lysine (Lys or K), leucine (Leu or L), methionine (Met or M), asparagine (Asn or N), proline (Pro or P), glutamine (Gin or Q), arginine (Arg or R), serine (Ser or S), threonine (Thr or T), valine (Vai or V), tryptophan (Trp or W), and tyrosine (Tyr or Y) residues. "Protecting group" refers to any atom or group of atoms added to a molecule to prevent undesired chemical reactions of existing groups within the molecule. A "protecting group" may be an unstable chemical moiety known in the art, which is used to protect reactive groups such as hydroxyl, amino and thiol groups to prevent undesired or premature reactions during chemical synthesis. Protecting groups are typically used selectively and / or orthogonally to protect sites during the reactions of other reactive sites, which can then be removed to leave the unprotected groups intact or available for further reactions. A non-limiting list of protecting groups include benzyl; substituted benzyl; alkylcarbonyls and alkoxycarbonyls (e.g., t-butoxycarbonyl (BOC), acetyl, or isobutyryl); arylalkylcarbonyls and arylalkoxycarbonyls (e.g., benzyloxycarbonyl); substituted methyl ether (e.g. methoxymethyl ether); substituted ethyl ether; a substituted benzyl ether; tetrahydropyranyl ether; silyls (e.g., trimethylsilyl, triethylsilyl, triisopropylsilyl, t-butyldimethylsilyl, tri-iso-propylsilyloxymethyl, [2-(trimethylsilyl)ethoxy]methyl or t-butyldiphenylsilyl); esters (e.g. benzoate ester); carbonates (e.g. methoxymethylcarbonate); sulfonates (e.g. tosylate or mesylate); acyclic ketal (e.g. dimethyl acetal); cyclic ketals (e.g., 1,3-dioxane, 1,3-dioxolanes, and those described herein); acyclic acetal; cyclic acetal (e.g., those described herein); acyclic hemiacetal; cyclic hemiacetal; cyclic dithioketals (e.g., 1,3-dithiane or 1,3-dithiolane); orthoesters (e.g., those described herein) and triarylmethyl groups (e.g., trityl; monomethoxytrityl (MMTr); 4,4'-dimethoxytrityl (DMTr); 4,4',4"-trimethoxytrityl (TMTr); and those described herein). Preferred protecting groups are selected from acetyl (Ac), benzoyl (Bzl), benzyl (Bn), isobutyryl (iBu), phenylacetyl, benzyloxymethyl acetal (BOM), beta-methoxyethoxymethyl ether (MEM), methoxymethylether (MOM), p-methoxybenzyl ether (PMB), methylthiomethyl ether, pivaloyl (Piv), tetrahydropyranyl (THP), triphenylmethyl (Trt), methoxytrityl [(4-methoxyohenyl)diphenylmethyl-] (MMT), dimethoxytrityl, [bis-(4-methoxyphenyl)phenylmethyl (DMT), trimethylsilyl ether (TMS), tert-butyldimethylsilyl ether (TBDMS), tri-iso-propylsilyloxymethyl ether (TOM), triisopropylsilyl ether (TIPS), methyl ethers, ethoxyethyl ethers (EE) N,N-dimethylformamidine and 2-cynaonethyl (CE). "Hydroxy-protecting group" refers to a group that can prevent a hydroxyl from undergoing chemical reactions and can be removed under specific conditions to restore the hydroxyl. The main hydroxy-protecting groups include silane-type, acyl-type, or ether-type protecting groups, preferably the following: trimethylsilyl (TMS), triethylsilyl (TES), dimethylisopropylsilyl (DMIPS), diethylisopropylsilyl (DEIPS), tert-butyldimethylsilyl (TBDMS), tertbutyldiphenylsilyl (TBDPS), triisopropylsilyl (TIPS), acetyl (Ac), chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl (TFA), benzoyl, p-methoxybenzoyl, 9-fluorenylmethoxycarbonyl (Fmoc), allyloxycarbonyl (Alloc), 2,2,2-trichloroethoxycarbonyl (Troc), benzyloxycarbonyl (Cbz), tert-butoxycarbonyl (Boc), benzyl (Bn), p-methoxybenzyl (PMB), allyl, triphenylmethyl (Tr), di-p-methoxytrityl (DMTr), methoxymethyl (MOM), benzyloxymethyl (BOM), 2,2,2-trichloroethoxymethyl, 2-methoxyethoxymethyl (MEM), methylthiomethyl (MTM), p-methoxybenzyloxymethyl (PMBM), -C(O)CH2CH2C(O)OH or 4,4'-dimethoxytrityl, preferably -C(O)CH2CH2C(O)OH or 4,4'-dimethoxytrityl, more preferably -C(O)CH2CH2C(O)OH. As used herein, the term "pharmaceutically acceptable salt" represents carboxylates or amino acid salts of a compound of the present invention, which are suitable for contact with patient tissues within the scope of sound medical judgment without causing excessive toxicity, irritation, allergic reactions, etc., and are effective in terms of the intended use with a reasonable benefit / risk ratio; said salt includes, where applicable, the zwitterionic form of a compound of the present invention. The present invention includes tautomers, which are functional-group isomers resulting from the rapid migration of an atom in a molecule between two positions. A compound with different tautomeric forms, said herein, refers to all the tautomers and does not be restricted to any specific tautomeric form. A compound of the present invention may include one or more asymmetric centers, and thus may exist in various stereoisomeric forms, such as enantiomers and / or diastereomers. For example, a compound of the present invention may be one of the forms of enantiomer, diastereoisomer or geometric isomer (e.g. a cis isomer or a trans isomer), or may be a mixture of any type of stereoisomerism, including a racemic mixture and a mixture enriched with one or more forms of stereoisomer. The present invention contemplates all such compounds, including cis and trans isomers, (-)- and (+)-enantiomers, (R)- and (S)-enantiomers, diastereomers, (D)-isomers, (L)-isomers, and racemic and other mixtures thereof, such as enantiomeric or diastereomerically enriched mixtures, all of which are within the scope of the present invention. Herein, for a compound or linking structure containing a chiral center, it may be in the (S) absolute configuration, or in the (R) absolute configuration, or a mixture of both, i.e., a racemic form. An isomer herein may be achieved by separating from a mixture via any method known to those skilled in the art, wherein the method includes chiral high-pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; alternatively, a preferred isomer may be prepared through asymmetric synthesis. The present invention also includes isotopically labeled compounds (isotopic variants) which are equivalent to those described by formula (I), except that one or more atoms are replaced with atoms with an atomic mass or mass number different from that common in nature. Examples of isotopes which may be incorporated into a compound of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, such as 2H, 3H, 13C, nC, 14C, 15N, 18O,170,31P, 32P, 35S, 18F, and 36C1. Any compounds based on a compound of the present invention and containing any aforementioned isotope and / or any isotope of other atoms, the prodrugs thereof and the pharmaceutically acceptable salts of said compounds or said prodrugs all fall in the scope of the present invention. Certain isotopically labeled compounds of the present invention, such as a compound into which any radioisotope (e.g., 3H and 14C) is introduced, may be used for distribution determinations of a drug and / or the substrate tissue thereof. Tritium, i.e. 3H and carbon-14, i.e. 14C isotopes are particularly preferred, because they can be easily prepared and detected. Furthermore, substitution with an isotope heavier, such as deuterium, i.e. 2H, may in some cases be preferred because resultant increased metabolic stability may provide therapeutic benefits such as prolonged in vivo half-life or reduced dosage. An isotopically labeled compound of formula (I) of the present invention and the prodrug thereof may generally be prepared with any readily available isotopically labeled reagent instead of any non-isotopically labeled reagent, in a procedure described below and / or in a process disclosed in any of the Examples and Preparations. Compounds of the Present Invention The present invention relates to a compound of formula I or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof: Gi Si X S2 G2 q wherein Gi, G2, Si, S2, and X are as defined below. The present invention further relates to a cell comprising a compound as described above. The present invention further relates to a pharmaceutical composition comprising a compound as described above, or a cell as described above, and optionally a pharmaceutically acceptable carrier or excipient. The present invention further relates to a kit comprising a compound as described above, or a cell as described above. Gi and G2 In one embodiment, Gi and G2 are each independently a dsRNA. In another embodiment, Gi and G2 are each independently a siRNA. In another embodiment, Gi is a single-stranded RNA and G2 is a dsRNA. In another embodiment, Gi is a dsRNA and G2 is a single-stranded RNA. In one embodiment, Gi and G2 each target a different target mRNA. In another embodiment, Gi and G2 target an identical target mRNA. In a more specific embodiment, Gi and G2 are each independently a siRNA, and each sense strand is connected to a linker of the present invention and each targets a different target mRNA. In some embodiments, Gi and G2 may each optionally be conjugated to a ligand moiety. In a specific embodiment, the 5' end of Gi is conjugated to a ligand moiety. In a specific embodiment, the 3' end of G2 is conjugated to a ligand moiety. dsRNA and siRNA Both dsRNA and siRNA comprise a sense strand and an antisense strand. In some embodiments, substantially all nucleotides of the sense strand and substantially all nucleotides of the antisense strand are modified nucleotides. In some embodiments, at least 80% of the nucleotides of the sense strand are modified nucleotides, and / or at least 80%, at least 85%, at least 90%, at least 92%, and at least 95% of the nucleotides of the antisense strand are modified nucleotides. In some embodiments, at least 80% of the nucleotides of the antisense strand are modified nucleotides, and / or at least 80%, at least 85%, at least 90%, at least 92%, and at least 95% of the nucleotides of the sense strand are modified nucleotides. In some embodiments, all nucleotides of the sense strand and / or all nucleotides of the antisense strand are modified nucleotides. The modification of a nucleotide described in the present invention may be a modification at the phosphate group, ribose group, and / or base group of the nucleotide. In some specific embodiments, the sense strand and antisense strand each independently comprise one or more nucleotide modifications selected from the group consisting of: 2'-O-alkyl modified nucleotides (e.g., 2'-O-methyl modified nucleotide), 2'-methoxyethyl modified nucleotides, 2'-fhioro modified nucleotides, 2'-deoxy-modified nucleotides, inosine ribonucleotides, abasic nucleotides, inverted abasic deoxyribonucleotides, nucleotides containing a phosphorothioate group, vinylphosphonate modified nucleotides, locked nucleotides, unlocked nucleotides, 2'-amino modified nucleotides, 2'-C-alkyl modified nucleotides, 2'-O-allyl modified nucleotides, morpholino nucleotides, phosphoramidates, nucleotides containing a non-natural base, terminal nucleotides linked to a cholesteryl derivative or a dodecanoic acid bisdecylamide group, deoxyribonucleotides, 3'-terminal deoxythymine (dT) nucleotides, conformationally restricted nucleotides, constrained ethyl nucleotides, 2'-hydroxy modified nucleotides, nucleotides containing a methylphosphonic acid group, nucleotides containing 5'-phosphoric acid, nucleotides containing a 5'-phosphate mimetic, glycol nucleic acids (GNAs), and 2-O-(N-methylacetamide) modified nucleotides. In some preferred embodiments, the sense strand and antisense strand each independently comprise one or more nucleotide modifications selected from the group consisting of: 2'-O-methyl modified nucleotides, 2'-fluoro modified nucleotides, and nucleotides containing a phosphorothioate group. In some preferred embodiments, the sense strand and / or the antisense strand comprises at least two 2'-fhioro modified nucleotides. In some preferred embodiments, the sense strand and / or the antisense strand comprises at least eight 2'-O-methyl modified nucleotides. In some preferred embodiments, the 3' end and / or 5' end of the sense strand and / or the antisense strand comprises 1 to 5 phosphorothioate intemucleotide linkages, preferably 2 to 3 phosphorothioate intemucleotide linkages. In some embodiments, the antisense strand has a length of 21 nucleotides and has (i) (counting from the 5' end) 2'-O-methyl modified nucleotides at positions 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21, and 2'-fhioro modified nucleotides at positions 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20; and / or (ii) (counting from the 5' end) phosphorothioate intemucleotide linkages between nucleotide positions 1 and 2, between nucleotide positions 2 and 3, between nucleotide positions 19 and 20, and between nucleotide positions 20 and 21. In some embodiments, the antisense strand has a length of 21 nucleotides and has (i) (counting from the 5' end) an SCP modification at position 1; (ii) (counting from the 5' end) 2'-fluoro modifications at positions 2, 4, 6, 8, 10, 12, 14, 16, and 18; (iii) (counting from the 5' end) 2'-O-methyl modifications at positions 3, 5, 7, 9, 11, 13, 15,17, 19, 20, and 21; and / or (iv) (counting from the 5' end) phosphorothioate intemucleotide linkages between nucleotide positions 1 and 2, between nucleotide positions 2 and 3, between nucleotide positions 19 and 20, and between nucleotide positions 20 and 21. In some embodiments, the antisense strand has a length of 21 nucleotides and has (i) (counting from the 5' end) 2'-deoxy modifications at positions 2, 5, 7, and 12; (ii) (counting from the 5' end) an SCP modification at position 1; (iii) (counting from the 5' end) a 2'-fluoro modification at position 14; (iv) (counting from the 5' end) 2'-O-methyl modifications at positions 3, 4, 6, 8, 9, 10, 11, 13, 15, 16, 17, 18, 19, 20, and 21; and / or (v) (counting from the 5' end) phosphorothioate intemucleotide linkages between nucleotide positions 1 and 2, between nucleotide positions 2 and 3, between nucleotide positions 19 and 20, and between nucleotide positions 20 and 21. In some embodiments, the sense strand has a length of 19 nucleotides and has (i) (counting from the 5' end) 2'-O-methyl modified nucleotides at positions 1 to 6 and 10 to 19, and 2'-fluoro modified nucleotides at positions 7 to 9; and / or (ii) (counting from the 5' end) phosphorothioate intemucleotide linkages between nucleotide positions 1 and 2, between nucleotide positions 2 and 3, and between nucleotide positions 18 and 19. In some embodiments, the sense strand has a length of 19 nucleotides and has (i) (counting from the 5' end) 2'-O-methyl modified nucleotides at positions 1 to 6 and 10 to 19, and 2'-fluoro modified nucleotides at positions 7 to 9; and / or (ii) (counting from the 5' end) phosphorothioate intemucleotide linkages between nucleotide positions 1 and 2, between nucleotide positions 2 and 3, between nucleotide positions 17 and 18, and between nucleotide positions 18 and 19. Terminal modification In one embodiment, an end of the sense strand of each of Gi and G2 optionally contains one or more terminal modifications. In a specific embodiment, an end of the sense strand of each of Gi and G2 optionally contains a terminal modification; In another specific embodiment, the 5' end and / or 3' end of the sense strand of each of Gi and G2 optionally contains a terminal modification. In a specific embodiment, the 3' end of the sense strand of Gi and the 5' end of the sense strand of G2 contain a terminal modification. In a specific embodiment, the 5' end of the sense strand of Gi has no terminal modification; In another specific embodiment, the modification at the 5' end of the sense strand of Gi is GL34. In a specific embodiment, the 3' end of the sense strand of Gi has no terminal modification; In another specific embodiment, the modification at the 3' end of the sense strand of Gi is GL34; In another specific embodiment, the modification at the 3' end of the sense strand of Gi is IB. In a specific embodiment, the 5' end of the sense strand of G2 has no terminal modification; In another specific embodiment, the modification at the 5' end of the sense strand of G2 is GL34; In another specific embodiment, the modification at the 5' end of the sense strand of G2 is IB. In a specific embodiment, the 3' end of the sense strand of G2 has no terminal modification; In another specific embodiment, the modification at the 3' end of the sense strand of G2 is GL34; In another specific embodiment, the modification at the 3' end of the sense strand of G2 is GL6. In one embodiment, the terminal modification is an abasic nucleotide; In another embodiment, the terminal modification is an inverted nucleotide; In another embodiment, the terminal modification is optionally substituted N h , preferably substituted with a GalNAc-containing side chain substituent. In a preferred embodiment, the terminal modification is IB; In a preferred embodiment, the terminal modification is STM1; In a preferred embodiment, the terminal modification is GL34; In a preferred embodiment, the terminal modification is GL35; In a preferred embodiment, the terminal modification is GL36. Si and S2 In one embodiment, Si is a bond. In another embodiment, Si is -(OCH2CH2)k-, wherein k is an integer from 1 to 10, preferably 3 or 6. In another embodiment, Si is -(CH2CH2O)k-, wherein k is an integer from 1 to 10, preferably 3 or 6. In another embodiment, Si is -O(CH2CH2O)k-, wherein k is an integer from 1 to 10, preferably 3 or 6. In another embodiment, Si is -(CH2)k-, wherein k is an integer from 1 to 10. In one embodiment, S2 is a bond. In another embodiment, S2 is -(OCH2CH2)k-, wherein k is an integer from 1 to 10, preferably 3 or 6. In another embodiment, S2 is -(CH2CH2O)k-, wherein k is an integer from 1 to 10, preferably 3 or 6. In another embodiment, S2 is -O(CH2CH2O)k-, wherein k is an integer from 1 to 10, preferably 3 or 6. In another embodiment, S2 is -(CH2)k-, wherein k is an integer from 1 to 10. X In one embodiment, X is a bond. In one embodiment, X is Nt(dN)m, wherein Nt is selected from a deoxyribonucleotide, a ribonucleotide, a 2'- 5' ribonucleotide, or a 2'-5' deoxyribonucleotide, dN is each independently selected from dA, dT, dG, or dC, and m is 1, 2, 3, 4, or 5. In one embodiment, X is (G2p)dAdT; In another embodiment, X is rGdAdT; In another embodiment, X is dCdA; In another embodiment, X is dAdT; In another embodiment, X is dAdCdA; In another embodiment, X is dTdCdA; In another embodiment, X is dAdAdA; In another embodiment, X is dTdTdT; In another embodiment, X is dTdTdTdT; In another embodiment, X is dTdTdTdTdT. In one embodiment, X comprises one or more compounds selected from formula (1-1) or formula (1-2), or a tautomer or stereoisomer thereof, wherein ring A, Tg, Ra, Rb, Rc, w, Lo, Li, and L2 are as defined below; further, X may also comprise one or more Nt. In one embodiment, X comprises one or more compounds of formula II, or a tautomer or stereoisomer thereof, wherein Tg, Ra, Rb, Rc, Li, and L2 are as defined below; further, X may also comprise one or more Nt. In one embodiment, X comprises one or more compounds of formula III, or a tautomer or stereoisomer thereof, wherein Sg, L3, L4, and L5 are as defined below; further, X may also comprise one or more Nt. —Sg—L3  zL5x \ l4           (HI) In one embodiment, X comprises one or more compounds of formula Illa, or a tautomer or stereoisomer thereof, wherein L3, L4, and L5 are as defined below; further, X may also comprise one or more Nt. (Illa) In one embodiment, X comprises one or more compounds selected from the group consisting of: further, X may also comprise one or more Nt. In one embodiment, X is -(BL)p(dN)m, wherein BL is selected from a compound of formula (1-1), (1-2), (II), (III), or (Illa) as defined herein, or a tautomer or stereoisomer thereof, or from BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, BL9, BL10, BL11, or BL12, or a tautomer or stereoisomer thereof. In one embodiment, X is BL(dN)m, wherein BL is selected from BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, BL9, BL 10, BL 11 or BL 12, or a tautomer or stereoisomer thereof, preferably BL1, dN is each independently selected from dA, dT, dG, or dC, and m is 1, 2, 3, 4, or 5. In a preferred embodiment, X is BLl-dTdTdT or BL1-dCdA. In one embodiment, X is (BL)P, wherein BL is selected from BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, or BL9, and p is 1, 2, or 3. In a preferred embodiment, X is BL1; In a preferred embodiment, X is BL1-BL1-BL1; In a preferred embodiment, X is BL7; In a preferred embodiment, X is BL7-BL7-BL7; In a preferred embodiment, X is BL8; In a preferred embodiment, X is BL8-BL8-BL8; In a preferred embodiment, X is BL9; In a preferred embodiment, X is BL9-BL9-BL9; In a preferred embodiment, X is BL10; In a preferred embodiment, X is BL10-BL10-BL10; In apreferred embodiment, X is BL11; In apreferred embodiment, X is BL11-BL11-BL11. Ring A In one embodiment, ring A is C5-10 cycloalkyl; In another embodiment, ring A is 5-membered to 10-membered heterocyclyl; In another embodiment, ring A is Ce-io aryl, such as phenyl; In another embodiment, ring A is 5membered to 10-membered heteroaryl, such as pyridine. Tg or Sg In one embodiment, Tg is selected from -S-Rt, -S-S-Rt, or -OCH2-S-S-Rt, wherein each Rt is independently selected from H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, or a GalNAc-containing chain, and is optionally deuterated or fully deuterated. In one embodiment, Tg is -S-S-C(Rd)3 or -OCH2-S-S-C(Rd)3, wherein each Rd is independently selected from H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, or a GalNAc-containing chain, and is optionally deuterated or fully deuterated; In a specific embodiment, Tg is -S-S-C(CH3)3. In one embodiment, Tg is a sugar moiety; In a specific embodiment, Tg is a five-membered sugar; In another specific embodiment, Tg is a six-membered sugar; In a more specific embodiment, Tg is A'-acctylgalactosaminc OH                                                        OH HO <                                                           HO < H^y^oy ( nhac ); In a more specific embodiment, Tg is galactose ( OH ); In a more specific embodiment, Tg is A-acetylglucosamine; In a more specific embodiment, Tg is glucose; In a more specific embodiment, Tg is mannose; In a more specific embodiment, Tg is glucuronic acid; In a more specific embodiment, Tg is neuraminic acid (sialic acid); In a more specific embodiment, Tg is xylose; In a more specific embodiment, Tg is fucose. In one embodiment, Tg is a polypeptide; In one embodiment, Tg is a group comprising 1, 2, 3, 4, or 5 amino acid residues; In one embodiment, Tg is -(AA)a-R; In one embodiment, Tg is -NH(AA)a-R; In one embodiment, Tg is -(AA)a-C(O)R; In one embodiment, Tg is -NH(AA)a-C(O)R; In one embodiment, Tg is -C(O)-NH(AA)a-C(O)NR. In one embodiment, Sg is a sugar moiety; In a specific embodiment, Sg is a five-membered sugar; In another specific embodiment, Sg is a six-membered sugar; In a more specific embodiment, Sg is A'-acctylgalactosaminc o HO /                                              HO Ho^L-c^°~y                                      ho: nhac   ); In a more specific embodiment, Sg is galactose ( ,O on ); In a more specific embodiment, OH ho / hoXj^^oh Sg is galactosamine ( NH2 ), which is optionally substituted with -Ac, -C(O)-Ci-6 alkylene-OH, e.g. OH V^OH HN^_ O HO HO oh ; In a more specific embodiment, Sg is / V-acetylglucosamine; In a more specific embodiment, Sg is glucose; In a more specific embodiment, Sg is mannose; In a more specific embodiment, Sg is glucuronic acid; In a more specific embodiment, Sg is neuraminic acid (sialic acid); In a more specific embodiment, Sg is xylose; In a more specific embodiment, Sg is fucose. AA In one embodiment, AA is an amino acid residue; In another embodiment, AA is a natural amino acid residue; In another embodiment, AA is a valine residue; In another embodiment, AA is an alanine residue; In another embodiment, AA is a glycine residue; In another embodiment, AA is a leucine residue; In another embodiment, AA is an isoleucine residue. R In one embodiment, R is H; In another embodiment, R is Ci-6 alkyl; In another embodiment, R is Ci-6 haloalkyl. Lo In one embodiment, Lo is -NRc-; In another embodiment, Lo is C(O); In another embodiment, Lo is -OC(O)NRc-; In another embodiment, Lo is -C(O)NRc-; In another embodiment, Lo is -NRcC(O)-; In another embodiment, Lo is -NRc-C(O)O-; In another embodiment, Lo is -C(O)NRc-C(O)-. Li and L2 In one embodiment, Li is a bond; In another embodiment, Li is -(CH2)P-; In another embodiment, Li is -O-(CH2)P-; In another embodiment, Li is -(CH2)P-O-; In another embodiment, Li is -O-(CH2)p-O-(CH2)q-; In another embodiment, Li is -O-(CH2)P-NHCO-; In another embodiment, Li is -(OCH2CH2)P-; In another embodiment, Li is -(CH2CH2O)p-; In another embodiment, Li is -O(CH2CH2O)P-; In another embodiment, Li is -NHC(O)-; In another embodiment, Li is -C(O)NH-; In another embodiment, Li is -OC(O)-; In another embodiment, Li is -C(O)O-; In another embodiment, Li is -S-S-; In another embodiment, Li is -NHC(O)O-; In another embodiment, Li is -NHC(O)NH-; In another embodiment, Li is -OC(O)O-; In another embodiment, Li is -OC(O)NH-; In another embodiment, Li is -O-CH(CH(OH)CH2OH)-; In another embodiment, Li is -O-CH(CH(NH2)CH2OH)-; In another embodiment, Li is -O-CH(CH2OH)CH(OH)-; In another embodiment, Li is -NH-CH(CH2OH)CH(OH)-; In another embodiment, Li is -O-CH2CH(OH)CH(OH)-; In another embodiment, Li is -O-CH2CH(NH2)CH(OH)-; In another embodiment, Li is -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-; In another embodiment, Li is -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-; In another embodiment, Li is -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-; In another embodiment, Li is -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-; In another embodiment, Li is -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-; In another embodiment, Li is -NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-. In one embodiment, L2 is a bond; In another embodiment, L2 is -(CH2)P-; In another embodiment, L2 is -O-(CH2)p-; In another embodiment, L2 is -(CH2)P-O-; In another embodiment, L2 is -O-(CH2)p-O-(CH2)q-; In another embodiment, L2 is -O-(CH2)P-NHCO-; In another embodiment, L2 is -(OCH2CH2)P-; In another embodiment, L2 is -(CH2CH2O)p-; In another embodiment, L2 is -O(CH2CH2O)P-; In another embodiment, L2 is -NHC(O)-; In another embodiment, L2 is -C(O)NH-; In another embodiment, L2 is -OC(O)-; In another embodiment, L2 is -C(O)O-; In another embodiment, L2 is -S-S-; In another embodiment, L2 is -NHC(O)O-; In another embodiment, L2 is -NHC(O)NH-; In another embodiment, L2 is -OC(O)O-; In another embodiment, L2 is -OC(O)NH-; In another embodiment, L2 is -O-CH(CH(OH)CH2OH)-; In another embodiment, L2 is -O-CH(CH(NH2)CH2OH)-; In another embodiment, L2 is -O-CH(CH2OH)CH(OH)-; In another embodiment, L2 is -NH-CH(CH2OH)CH(OH)-; In another embodiment, L2 is -O-CH2CH(OH)CH(OH)-; In another embodiment, L2 is -O-CH2CH(NH2)CH(OH)-; In another embodiment, L2 is -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-; In another embodiment, L2 is -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-; In another embodiment, L2 is -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-; In another embodiment, L2 is -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-; In another embodiment, L2 is -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-; In another embodiment, L2 is -NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-. In one embodiment, Li and L2 are optionally substituted with 1,2, or 3 substituents selected from halogen, OH, NH2, -C1-6 alkylene OH, -C1-6 alkylene NH2, C1-6 alkyl, or C1-6 haloalkyl. In one embodiment, p = 1; In another embodiment, p = 2; In another embodiment, p = 3; In another embodiment, p = 4; In another embodiment, p = 5; In another embodiment, p = 6. In one embodiment, q = 1; In another embodiment, q = 2; In another embodiment, q = 3; In another embodiment, q = 4; In another embodiment, q = 5; In another embodiment, q = 6. In a more specific embodiment, Li is -O-(CH2)3-O-CH2-, and L2 is -(CH2)2-O-. L3 and L4 In one embodiment, L3 is a bond; In another embodiment, L3 is -(CH2)i-; In another embodiment, L3 is -O-(CH2)i-; In another embodiment, L3 is -(CH2)i-O-; In another embodiment, L3 is -O-(CH2)i-O-(CH2)j-; In another embodiment, L3 is -O-(CH2)i-NHCO-; In another embodiment, L3 is -(OCH2CH2)i-; In another embodiment, L3 is -(CH2CH2O)i-; In another embodiment, L3 is -O(CH2CH2O)i-; In another embodiment, L3 is -(CH2)j-(OCH2CH2)i-; In another embodiment, L3 is -NHC(O)-; In another embodiment, L3 is -C(O)NH-; In another embodiment, L3 is -C(O)-; In another embodiment, L3 is -OC(O)-; In another embodiment, L3 is -C(O)O-; In another embodiment, L3 is -S-S-; In another embodiment, L3 is -NHC(O)O-; In another embodiment, L3 is -NHC(0)NH-; In another embodiment, L3 is -OC(O)O-; In another embodiment, L3 is -OC(O)NH-; In another embodiment, In another embodiment, L3 is -O-CH(CH(OH)CH2OH)-; In another embodiment, L3 is -O-CH(CH(NH2)CH2OH)-; In another embodiment, L3 is -O-CH(CH2OH)CH(OH)-; In another embodiment, L3 is -NH-CH(CH2OH)CH(OH)-; In another embodiment, L3 is -O-CH2CH(OH)CH(OH)-; In another embodiment, L3 is -O-CH2CH(NH2)CH(OH)-; In another embodiment, L3 is -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-; In another embodiment, L3 is -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-; In another embodiment, L3 is -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-; In another embodiment, L3 is -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-; In another embodiment, L3 is -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-; In another embodiment, L3 is -NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-. In one embodiment, L4 is a bond; In another embodiment, L4 is -(CH2)i-; In another embodiment, L4 is -O-(CH2)i-; In another embodiment, L4 is -(CH2)i-O-; In another embodiment, L4 is -O-(CH2)i-O-(CH2)j-; In another embodiment, L4 is -O-(CH2)i-NHCO-; In another embodiment, L4 is -(OCH2CH2)i-; In another embodiment, L4 is -(CH2CH2O)i-; In another embodiment, L4 is -O(CH2CH2O)i-; In another embodiment, L4 is -(CH2)j-(OCH2CH2)i-; In another embodiment, L4 is -NHC(O)-; In another embodiment, L4 is -C(O)NH-; In another embodiment, L4 is -C(O)-; In another embodiment, L4 is -OC(O)-; In another embodiment, L4 is -C(O)O-; In another embodiment, L4 is -S-S-; In another embodiment, L4 is -NHC(O)O-; In another embodiment, L4 is -NHC(0)NH-; In another embodiment, L4 is -OC(O)O-; In another embodiment, L4 is -OC(O)NH-; In another embodiment, In another embodiment, L4 is -O-CH(CH(OH)CH2OH)-; In another embodiment, L4 is -O-CH(CH(NH2)CH2OH)-; In another embodiment, L4 is -O-CH(CH2OH)CH(OH)-; In another embodiment, L4 is -NH-CH(CH2OH)CH(OH)-; In another embodiment, L4 is -O-CH2CH(OH)CH(OH)-; In another embodiment, L4 is -O-CH2CH(NH2)CH(OH)-; In another embodiment, L4 is -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-; In another embodiment, L4 is -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-; In another embodiment, L4 is -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-; In another embodiment, L4 is -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-; In another embodiment, L4 is -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-; In another embodiment, L4 is -NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-. In one embodiment, i = 1; In another embodiment, i = 2; In another embodiment, i = 3; In another embodiment, i = 4; In another embodiment, i = 5; In another embodiment, i = 6. In one embodiment, j = 1; In another embodiment, j = 2; In another embodiment, j = 3; In another embodiment, j = 4; In another embodiment,] = 5; In another embodiment,] = 6. In a more specific embodiment, L3 is -O-(CH2)4-, and L4 is a bond. In a more specific embodiment, L3 is -O-(CH2)5-, and L4 is -OC(O)-. In a more specific embodiment, L3 is -O-(CH2)4, and L4 is -C(O)-. In a more specific embodiment, L3 is -(OCH2CH2)3-, and L4 is -NHC(O)-. In a more specific embodiment, L3 is -(OCH2CH2)3-, and L4 is -OC(O)-. L5 In one embodiment, L5 is a bond; In one embodiment, L5 is C3-7 cycloalkyl, such as C5-6 cycloalkyl; In one embodiment, L5 is Ce-io aryl; In one embodiment, L5 is 3-membered to 7-membered heterocyclyl, preferably 5membered to 6-membered heterocyclyl containing 1 to 3 heteroatoms; In one embodiment, L5 is 5-membered to 10-membered heteroaryl, such as 5-membered to 6-membered heteroaryl containing 1 to 3 heteroatoms. In one embodiment, the heteroatom is N; In one embodiment, the heteroatom is O; In a more specific embodiment, L5 is In a more specific embodiment, L5 is In a more specific embodiment, L5 is a Ra, Rb and Rc In one embodiment, Ra is H; In another embodiment, Ra is D; In another embodiment, Ra is halogen; In another embodiment, Ra is C1-6 alkyl; In another embodiment, Ra is C1-6 haloalkyl. In one embodiment, Rb is H; In another embodiment, Rb is D; In another embodiment, Rb is halogen; In another embodiment, Rb is C1-6 alkyl; In another embodiment, Rb is C1-6 haloalkyl. In one embodiment, Rc is H; In another embodiment, Rc is D; In another embodiment, Rcis halogen; In another embodiment, Rc is C1-6 alkyl; In another embodiment, Rc is C1-6 haloalkyl. In a more specific embodiment, Ra is H, Ra is H, and Rc is methyl. w In one embodiment, w is 0, 1, 2, 3, or 4. Any technical solution or any combination thereof in any of the above specific embodiments can be combined with any technical solution or any combination thereof in other specific embodiments. The present invention is intended to include all combinations of these technical solutions, which are not listed one by one due to space limitations. The present invention relates specifically to a compound of formula (I) or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof: G1 Si X S2 G2 q) wherein Gi and G2 are each independently a nucleic acid molecule; Si and S2 are each independently a bond, -(OCH2CH2)k-, -(CH2CH2O)k-, -O(CH2CH2O)k-, or -(CH2)k-; k is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; X is a linker; preferably, Si and S2 are each independently a bond or -O(CH2CH2O)k-, wherein k is 1, 2, 3, 4, 5, 6, 7, or 8; preferably, Si and S2 are each independently abend, -O(CH2CH2O)3-, or -O(CH2CH2O)6-. The present invention relates to a compound of formula (I) described above, wherein X comprises one or more compounds selected from formula (1-1) or formula (1-2), or a tautomer or stereoisomer thereof: , Ra Rb Ra Rb                Li V 1 y A .J z Tg                       (i-i) Tg                         (1-2) wherein, ring A is selected from C5-10 cycloalkyl, 5-membered to 10-membered heterocyclyl, Ce-io aryl, or 5-membered to 10-membered heteroaryl, preferably Ce-io aryl or 5-membered to 10-membered heteroaryl; Tg is selected from -S-Rt, -S-S-Rt, -OCH2-S-S-Rt, a sugar moiety, or a polypeptide; Rt is selected from H, C1-6 alkyl, or C1-6 haloalkyl; the sugar moiety is a sugar that can be cleaved in the inclusion or lysosome, preferably a five- or six-membered sugar; the polypeptide is a group comprising 1, 2, 3, 4, or 5 amino acid residues; Lo is selected from -NRc-, C(O), -OC(O)NRc-, -C(O)NRc-, -NRcC(O)-, -NRc-C(O)O-, or -C(O)NRc-C(O)-; Li and L2 are linkers, preferably each independently selected from a bond, -(CH2)P-, -O-(CH2)P-, -(CH2)P-O-, -O-(CH2)P-O-(CH2)q-, -O-(CH2)p-NHCO-, -(CH2)q-(OCH2CH2)P-, -(CH2CH2O)P-, -O(CH2CH2O)P-, -NHC(O)-, -C(O)NH-, -OC(O)-, -C(O)O-, -S-S-, -NHC(O)O-, -NHC(O)NH-, -OC(O)O-, -OC(O)NH-, -O-CH(CH(OH)CH2OH)-, -O-CH(CH(NH2)CH2OH)-, -O-CH(CH2OH)CH(OH)-, -NH-CH(CH2OH)CH(OH)-, -o-CH2CH(OH)CH(OH)-, -O-CH2CH(NH2)CH(OH)-, -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-, -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-, -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-, or-NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-; Li and L2 are optionally substituted with 1, 2, or 3 substituents selected from halogen, OH, NH2, -C1-6 alkylene OH, -C1-6 alkylene NH2, C1-6 alkyl, or C1-6 haloalkyl; p and q are each independently 1, 2, 3, 4, 5, or 6; wherein and in formula (1-1) and formula (1-2) are connected to Gi or G2 via a bridged linkage; preferably represents connection to Gi via a bridged linkage (Si), and in formula (1-1) and formula (I-2) represents connection to G2 via a bridged linkage (S2); w is selected from 0, 1, 2, 3, or 4; Ra, Rb, and Re are independently selected from H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, and are optionally deuterated or fully deuterated. The present invention relates to a compound of formula (I) described above, wherein X comprises one or more compounds of formula (II), or a tautomer or stereoisomer thereof: wherein Tg is -S-S-C(Rd)3, -OCH2-S-S-C(Rd)3, a sugar moiety, or a polypeptide; the sugar moiety is preferably a sugar that can be cleaved in the inclusion or lysosome, preferably a five- or six-membered sugar, more preferably a six-membered sugar, more preferably selected from A-acetylgalactosamine, galactose, A-acetylglucosamine, glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose; the polypeptide is selected from -(AA)a-R, -NH(AA)a-R, -(AA)a-C(O)R, -NH(AA)a-C(O)R, or -C(O)-NH(AA)a-C(O)NR; wherein each AA is independently selected from amino acid residues, preferably each AA is independently selected from natural amino acid residues; a is selected from 1, 2, 3, or 4; R is selected from H, D, halogen, Ci-6 alkyl, or Ci-6 haloalkyl, wherein R may be optionally deuterated or fully deuterated; Ra, Rb, and Re are independently selected from H, D, halogen, Ci-6 alkyl, or Ci-6 haloalkyl, and are optionally deuterated or fully deuterated; each Ra is independently selected from H, D, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, or a GalNAc-containing chain, and is optionally deuterated or fully deuterated; wherein Li and L2 are linkers, preferably each independently selected from a bond, -(CH2)P-, -O-(CH2)P-, -(CH2)p-O-, -O-(CH2)p-O-(CH2)q-, -O-(CH2)p-NHCO-, -(OCH2CH2)p-, -(CH2CH2O)p-, -O(CH2CH2O)p-, -NHC(O)-, -C(O)NH-, -OC(O)-, -0(0)0-, -S-S-, -NHC(0)0-, -NHC(0)NH-, -00(0)0-, -0C(0)NH-, -0-CH(CH(0H)CH20H)-, -O-CH(CH(NH2)CH2OH)-, -0-CH(CH20H)CH(0H)-, -NH-CH(CH20H)CH(0H)-, -o-CH2CH(0H)CH(0H)-, -O-CH2CH(NH2)CH(OH)-, -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-, -NHC(0)-CH2-0-CH(CH(NH2)CH2OH)-, -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-, or-NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-; wherein p and q are each independently 1, 2, 3, 4, 5, or 6; wherein and in formula (II) are connected to Gi or G2 via a bridged linkage; preferably represents connection to Gi via a bridged linkage (Si), and in formula (II) represents connection to G2 via a bridged linkage (S2); preferably, Tg is selected from -S-S-C(Rd)3, -OCH2-S-S-C(Rd)3, a sugar moiety, or a polypeptide; the sugar moiety is selected from A-acctylgalactosaminc. galactose, A-acetylghicosamine, glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose; the polypeptide is -NH(AA)a-C(0)R; each AA is independently selected from a valine residue, an alanine residue, a glycine residue, a leucine residue, or an isoleucine residue, more preferably from a valine residue or an alanine residue; a is selected from 1, 2, or 3, preferably 2 or 3; R is selected from H, D, C1-6 alkyl, or C1-6 haloalkyl, preferably C1-6 alkyl, such as CH3; Ra, Rb, and Re are each independently selected from H, D, C1-6 alkyl, or C1-6 haloalkyl, preferably H or C1-6 alkyl, such as H or CH3; each Ra is independently selected from H, D, C1-6 alkyl, or C1-6 haloalkyl, preferably C1-6 alkyl, such as CH3; Li is selected from -(CH2)P-, -0-(CH2)P-, -(CH2)P-0-, -O-(CH2)P-O-(CH2)q-, -0-(CH2)P-NHC0-, - (OCH2CH2)p-, -(CH2CH2O)p-, or -O(CH2CH2O)P-, preferably -O-(CH2)P-O-(CH2)q-, or -0-(CH2)P-NHC0-; L2 is selected from -(CH2)P-, -0-(CH2)P-, -(CH2)P-0-, -O-(CH2)P-O-(CH2)q-, -0-(CH2)P-NHC0-, - (OCH2CH2)p-, -(CH2CH2O)p-, or -O(CH2CH2O)P-, preferably -(CH2)P-0-; each p is independently selected from 2, 3, 4, 5, or 6, preferably 4, 5, or 6; each p is independently selected from 1, 2, 3, 4, or 5, preferably 1, 2, or 3; represents connection to Gi via a bridged linkage (Si), and in formula (II) represents connection to G2 via a bridged linkage (S2); more preferably, Tg is selected from A-acetylgalactosamine, galactose, A-acctylglucosaminc. glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose; Ra, Rb, and Rc are each independently selected from H, D, C1-6 alkyl, or C1-6 haloalkyl, preferably H or C1-6 alkyl, such as H or CH3; each Rd is independently selected from H, D, C1-6 alkyl, or C1-6 haloalkyl, preferably C1-6 alkyl, such as C(CH3)3; Li is selected from -(CH2)P-, -0-(CH2)P-, -(CH2)P-0-, -O-(CH2)P-O-(CH2)q-, -0-(CH2)P-NHC0-, - (OCH2CH2)p-, -(CH2CH2O)p-, or -O(CH2CH2O)P-, preferably -O-(CH2)P-O-(CH2)q-, or -0-(CH2)P-NHC0-; L2 is selected from -(CH2)P-, -0-(CH2)P-, -(CH2)P-0-, -O-(CH2)P-O-(CH2)q-, -0-(CH2)P-NHC0-, - (OCH2CH2)p-, -(CH2CH2O)p-, or -O(CH2CH2O)P-, preferably -(CH2)P-O-; each p is independently selected from 2, 3, 4, 5, or 6, preferably 4, 5, or 6; each p is independently selected from 1, 2, 3, 4, or 5, preferably 1, 2, or 3; represents connection to Gi via a bridged linkage (Si), and in formula (II) represents connection to G2 via a bridged linkage (S2). The present invention relates to a compound of formula (I) described above, wherein X comprises one or more compounds of formula (1-1), formula (1-2), or formula (II), or a tautomer or stereoisomer thereof, provided that: i) Tg is -S-S-C(CH3)3; ii) Tg is galactose, glucose, / V-acetylgalactosamine, or / / -acetylghicosamine, preferably galactose ( on ) or / / -acetylgalactosamine ( NHAc ); or 3) Tg is -NH(AA)a-C(O)R, such as H o = H • wherein each AA is independently selected from valine or alanine; a is selected from 1, 2, or 3, preferably 2 or 3; R is selected from H or Ci-6 alkyl, such as CH3; The present invention relates to a compound of formula (I) described above, wherein X comprises one or more compounds of formula (1-1), formula (1-2), or formula (II), or a tautomer or stereoisomer thereof, wherein Ra, Rb, and Rc are each independently selected from H, D, halogen, or Ci-6 alkyl, Li and L2 are each independently selected from a bond, -(CH2)P-, -O-(CH2)P-, -(CH2)P-O-, -O-(CH2)p-O-(CH2)q-, or -O-(CH2)P-NHCO-, and p and q are each independently 1, 2, 3, 4, 5, or 6. The present invention relates to a compound of formula (I) described above, wherein X comprises one or more compounds of formula (III), or a tautomer or stereoisomer thereof: wSg-L3x l5x \ L4 "O X (HI) wherein Sg is a sugar moiety, preferably a sugar that can be cleaved in the inclusion or lysosome, preferably a five- or six-membered sugar, more preferably a six-membered sugar, more preferably selected from N-acetylgalactosamine, galactosamine, galactose, / / -acetylghicosamine, glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose; L3 and L4 are linkers, preferably each independently selected from a bond, -(CH2)i-, -O-(CH2)i-, -(CH2)i-O-, -O-(CH2)i-O-(CH2)j-, -O-(CH2)i-NHCO-, -(OCH2CH2)i-, -(CH2CH2O)i-, -O(CH2CH2O)i-, -(CH2)j-(OCH2CH2)i-, -NHC(O)-, -C(O)NH-, -OC(O)-, -C(O)O-, -S-S-, -NHC(O)O-, -NHC(O)NH-, -OC(O)O-, -OC(O)NH-, -O-CH(CH(OH)CH2OH)-, -O-CH(CH(NH2)CH2OH)-, -O-CH(CH2OH)CH(OH)-, -NH-CH(CH2OH)CH(OH)-, -o-CH2CH(OH)CH(OH)-, -O-CH2CH(NH2)CH(OH)-, -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-, -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-, -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-, or-NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-; wherein i and j are each independently 1, 2, 3, 4, 5, or 6; L5 is a linker, preferably selected from a bond, C3-7 cycloalkyl, Ce-io aryl, 3-membered to 7-membered heterocyclyl, or 5-membered to 10-membered heteroaryl, more preferably, L5 is selected from a bond, C5-6 cycloalkyl, Ce-io aryl, 5-membered to 6-membered heterocyclyl containing 1 to 3 heteroatoms, or 5-membered to 6-membered heteroaryl containing 1 to 3 heteroatoms, wherein the heteroatom is N or 0; wherein and in formula (III) are connected to Gi or G2 via a bridged linkage; preferably represents connection to Gi via a bridged linkage (Si), and in formula (III) represents connection to G2 via a 22 bridged linkage (S2); preferably, Sg is selected from N-acetylgalactosamine, galactosamine, galactose, N-acetylglucosamine, glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose; L3 is selected from a bond, -(CH2)i-, -O-(CH2)i-, -(CH2)i-O-, -O-(CH2)i-O-(CH2)j-, -O-(CH2)i-NHCO-, -(OCH2CH2)i-, -(CH2CH2O)i-, -O(CH2CH2O)i-, or -(CH2)j-(OCH2CH2)i-; L4 is selected from a bond , -(CH2)i-, -O-(CH2)i-, -(CH2)i-O-, -O-(CH2)i-O-(CH2)j-, -O-(CH2)i-NHCO-, -(OCH2CH2)i-, -(CH2CH2O)i-, -O(CH2CH2O)i-, -NHC(O)-, -C(O)NH-, -OC(O)-, -C(O)O-, -S-S-, -NHC(O)O-, -NHC(O)NH-, -OC(O)O-, or -OC(O)NH-; each i is independently selected from 1, 2, 3, 4, 5, or 6; each j is independently selected from 1, 2, 3, 4, 5, or 6; L5 is selected from a bond, C5-6 cycloalkyl, Ce-io aryl, 5-membered to 6-membered heterocyclyl containing 1 to 3 heteroatoms, or 5-membered to 6-membered heteroaryl containing 1 to 3 heteroatoms, wherein the heteroatom is N or 0; represents connection to Gi via a bridged linkage (Si), and in formula (III) represents connection to G2 via a bridged linkage (S2). The present invention relates to a compound of formula (I) described above, wherein X comprises one or more compounds of formula (Illa), or a tautomer or stereoisomer thereof: O HO / _ L3 L5 H0 NHAc (Illa) L3 is selected from a bond, -(CH2)i-, -(CH2)i-O-, -O-(CH2)i-O-(CH2)j-, -(OCH2CH2)i-, -(CH2CH2O)i-, -O(CH2CH2O)i-, or -(CH2)j-(OCH2CH2)i-; L4 is selected from a bond, -NHC(O)-, -C(O)NH-, -OC(O)-, -C(O)O-, -S-S-, -NHC(O)O-, -NHC(0)NH-, -OC(O)O-, or -0C(0)NH-; L5 is selected from a bond, C5-6 cycloalkyl, or 5-membered to 6-membered heterocyclyl containing 1 to 3 heteroatoms, wherein the heteroatom is N or 0; wherein i and j are each independently 1, 2, 3, 4, 5, or 6; represents connection to Gi via a bridged linkage (Si), and to G2 via a bridged linkage (S2). in formula (Illa) represents connection The present invention relates to a compound of formula (I) described above, provided that: i)L3 is -(CH2)4-, L4 is a bond, and L5 is a bond; ii)L3 is -(CH2)s-, L4 is -OC(O)-, and L5 is iii)L3 is -(CH2)4-, L4 is -C(O)-, and L5 is iv)L3 is -CH2CH2-(OCH2CH2)2-, L4 is -NHC(O)-, and L5 is v)L3 is -CH2CH2-(OCH2CH2)2-, L4 is -OC(O)-, and L5 is The present invention relates to a compound of formula (I) described above, wherein X comprises one or more of the following compounds: Compound No. Structure BL1 o , OH                y oU 1 OH BL2 % O J « / co         ( T >° —z ^0 BL3 H N^° o OH H\G JU 1 ho\>2-^0 OH BL4 0 0         0 1 0 = BL5 0^ \ / S.     JL / O. / s       y BL6 0 H cn-w BL7 ^0 \Uv^ HO    NHAc           ' BL8 0                _ "° jL X BL9 OH                 x UwxUR H° H^.         O oz '--\ Qjw BL10 ^X^O^^O^ H° NHAC                 H I J. \ 'O^ BL11 I                    „ HOX° 0      0 A HO NHAC                A / o~y BL12 0 nXo. OJ J ।    7 ho\>2-X / 0 NHAc wherein represents connection to Gi via a bridged linkage (Si), and * represents connection to G2 via a bridged linkage (S2); The present invention relates to a compound of formula (I) described above, wherein X is a nucleotide linker, the nucleotide is selected from one or more of a deoxyribonucleotide, a ribonucleotide, a 2'-deoxy-2'-fluororibonucleotide, a 2'-5' ribonucleotide, and a 2'-5' deoxyribonucleotide. The present invention relates to a compound of formula (I) described above, wherein X is Nt(dN)m, wherein Nt is selected from a bond, a deoxyribonucleotide, a ribonucleotide, a 2'-deoxy-2'-fluororibonucleotide, or a 2'-5' ribonucleotide, each dN is independently selected from dA, dT, dG, or dC, and m is 1,2,3,4, 5, 6, 7, or 8, preferably m is 1, 2, 3, 4, or 5. The present invention relates to a compound of formula (I) described above, wherein X is selected from (G2p)dAdT, rGdAdT, dCdA, dAdT, dAdCdA, dTdCdA, dAdAdA, dTdTdT, -GfAIUf-, dTdTdTdT, or dTdTdTdTdT, preferably selected from (G2p)dAdT, rGdAdT, dCdA, dAdT, dAdCdA, dTdCdA, dAdAdA, dTdTdT, dTdTdTdT, or dTdTdTdTdT. The present invention relates to a compound of formula (I) described above, wherein X is -(BL)p(dN)m-; wherein each BL is independently selected from a compound of formula (1-1) or (1-2), a compound of formula (II), or a compound of formula (III) as defined herein, or a tautomer or stereoisomer thereof, or BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, BL9, BL10, BL11, or BL12, or a tautomer or stereoisomer thereof; each dN is independently selected from dA, dT, dG, or dC; p is selected from 0, 1, 2, 3, 4, 5, or 6, preferably 0, 1, 2, or 3; m is selected from 0, 1, 2, 3, 4, 5, 6, 7, or 8, preferably 0, 1, 2, 3, 4, or 5; p and m are not both 0; preferably, X is -(BL)P-; wherein each BL is independently selected from a compound of formula (1-1) or (1-2), a compound of formula (II), or a compound of formula (III) as defined herein, or a tautomer or stereoisomer thereof, or BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, BL9, BL10, BL11, or BL12, or a tautomer or stereoisomer thereof; p is selected from 0, 1, 2, 3, 4, 5, or 6, preferably 0, 1, 2, or 3. The present invention relates to a compound of formula (I) described above, provided that: i) X is BL(dN)m, wherein BL is selected from BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, BL9, BL10, BL11, or BL 12, preferably BL1, dN is each independently selected from dA, dT, dG, or dC, and m is 1, 2, 3, 4, or 5; ii) X is selected from BL 1-dTdTdT or BLl-dCdA; iii) X is (BL)P, wherein each BL is independently selected from BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, or BL9, preferably BL7 or BL8, and p is 1, 2, or 3; or iv) X is BL1, -BL 1-BL 1-BL 1-, BL5, BL7, BL8, BL9, BL10, BL11, BL12, BL7-BL7-BL7, BL8-BL8-BL8, or BL9-BL9-BL9, preferably X is BL7, BL7-BL7-BL7, BL8, BL8-BL8-BL8, BL9, or BL9-BL9-BL9. The present invention relates to a compound of formula (I) described above, wherein Gi and G2 are independently selected from a double-stranded nucleic acid molecule, preferably a dsRNA. The present invention relates to a compound of formula (I) described above, wherein the dsRNA molecule has a sense strand and an antisense strand, each having 14 to 30 nucleotides, wherein the antisense strand comprises a sequence sufficiently complementary to the sense strand and the target mRNA. The present invention relates to a compound of formula (I) described above, wherein Gi and G2 may target identical or different target mRNAs, preferably different target mRNAs. The present invention relates to a compound of formula (I) described above, wherein Gi and G2 each have a sense strand connected to -S1-X-S2-. The present invention relates to a compound of formula (I) described above, wherein the end of the sense strand of each of Gi and G2 optionally contains one or more terminal modifications, preferably the 5' end and / or 3' end of the sense strand of each of Gi and G2 optionally contains one or more terminal modifications. The present invention relates to a compound of formula (I) described above, wherein the 5' end of the sense 5 strand of Gi and the 5' end of the sense strand of G2 each contain an terminal modification. The present invention relates to a compound of formula (I) described above, wherein the terminal modification is selected from an abasic nucleotide (such as IB), an inverted nucleotide, and an optionally substituted y                                    0 Y y 0 h , preferably the optionally substituted          h         is substituted with a GalNAc- containing side chain substituent. 10 The present invention relates to a compound of formula (I) described above, wherein the terminal modification is selected from IB, STM1, or GL34. The present invention relates to a compound of formula (I) described above, wherein the 3' end of the antisense strand of each of Gi and G2 is a blunt end or overhang, preferably an overhang, more preferably an overhang of both nucleotides. 15 The present invention relates to a compound of formula (I) described above, wherein X, Si, and S2 are as defined in Table A, preferably X, Si, S2, 5' terminal modification of Gi, 3' terminal modification of Gi, 5' terminal modification of G2, and 3' terminal modification of G2 are as defined in Table A: Table A No. X SbS2 5' Terminal Modification of Gi 3' Terminal Modification ofGi 5' Terminal Modification ofG2 3' Terminal Modification ofG2 1 rGdAdT Bond None None None GL6 2 -dTdTdT- Bond None None None GL6 3 -(G2P)dAdT- Bond None None None GL6 4 -BL1- Bond None IB IB GL6 5 -BL1-BL1-BL1- Bond None None None GL6 6 -dTdTdTdT- Bond None None None GL6 7 -dTdTdTdTdT- Bond None None None GL6 8 -dTdTdT- Bond None None None GL6 9 -dTdTdT- Bond None IB IB GL6 10 -dAdAdA- Bond None None None GL6 11 -dTdCdA- Bond None None None GL6 12 -dCdA- Bond None None None GL6 13 -BL5- Bond None None None GL6 14 -GfAfUf- Bond None None None GL6 15 -dTdTdTdT- Bond None IB IB GL6 16 -dCdA- Bond None IB IB GL6 17 -dAdCdA- Bond None IB IB GL6 18 -BL1-dTdTdT- Bond None IB IB GL6 19 -BLl-dCdA- Bond None None None GL6 20 -BL7- Bond None None None GL6 21 -BL7-BL7-BL7- Bond None None None GL6 22 -BL8-BL8-BL8- Bond None None None GL6 23 -BL8- Bond None None None GL6 24 -BL9- Bond None None None GL6 25 -BL12- Bond None IB IB GL6 26 -BL7- Bond None IB IB GL6 27 -BL8- Bond None IB IB GL6 28 -BL1- Bond None None None GL6 29 -BL1- Si is a bond S2        is        - O(CH2CH2O)6- None None None GL6 30 -BL1- Si         is         - O(CH2CH2O)6- S2 is a bond None None None GL6 31 -BL1- Bond GL34 GL34 GL34 GL34 32 -BL1- Bond GL34 GL34 GL34 GL34 33 -BL7- Bond GL34 GL34 GL34 GL34 34 -BL12- Bond None IB IB GL6 35 -BL7- Bond None IB IB GL6 36 -BL8- Bond None IB IB GL6 37 -BL1- Bond None None None GL6 38 -BL1- Si is a bond S2        is        - O(CH2CH2O)6- None None None GL6 39 -BL1- Bond GL34 GL34 GL34 GL34 40 -BL1- Bond GL34 GL34 GL34 GL34 41 -BL7- Bond GL34 GL34 GL34 GL34 42 -BL1- Si         is         - O(CH2CH2O)3- S2 is a bond None None None GL6 43 -BL1- Si         is         - O(CH2CH2O)6- S2        is        - O(CH2CH2O)6- None None None GL6 44 -BL10- Si         is         - O(CH2CH2O)6- S2 is a bond None None None GL6 45 -BL11- Si         is         - O(CH2CH2O)6- S2 is a bond None None None GL6 46 Bond Si         is         - O(CH2CH2O)6- S2 is a bond None None None GL6 wherein, the structures of BL1 to BL 12 are as defined herein; the 5' and 3' terminal modifications of Gi and G2 are connected to Gi and G2 via a phosphate group or a phosphorothioate group; when located at the 5' end of Gi, GL34 represents when located at the 3' end of G2, GL34 represents or at the 5' end HO^ • of G2, GL34 represents when located at the 3' end IB is The present invention also provides a vector comprising a nucleotide sequence encoding the siRNA of the invention. The vector of the present invention can amplify or express a nucleotide encoding the siRNA of the invention linked thereto. For example, a siRNA targeting the PCSK9 gene can be expressed from a transcription unit inserted into a DNA or RNA vector. Expression can be transient (within hours to weeks) or sustained (weeks to months or longer), depending on the particular construct used and the target tissue or cell type. A nucleotide encoding the siRNA can be introduced into a linear construct, a circular plasmid, or a viral vector. A nucleotide encoding the siRNA can be stably expressed by integration into the cell genome, or can be stably inherited and expressed extrachromosomally. Generally speaking, a vector expressing the siRNA is usually a DNA plasmid or a viral vector. Viral vector systems comprising a sequence encoding the siRNA include, but are not limited to: (a) adenoviral vectors; (b) retroviral vectors; (c) adeno-associated viral vectors; (d) herpes simplex virus vectors; (e) SV40 vectors; (f) polyomavirus vectors; (g) papillomavirus vectors; (h) picomavirus vectors; (i) poxvirus vectors; and (j) helper virus-dependent or gutless adenoviral vectors. The present invention also provides a cell comprising the siRNA or vector of the invention, wherein the siRNA or vector of the invention can be transcribed in the cell. The present invention further relates to the use of a compound of formula (I) for the manufacture of a medicament for treating and / or preventing diseases. The present invention further provides a method for treating and / or preventing diseases comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I). The present invention further relates to a compound of formula (I) for use in the manufacture of a medicament for treating and / or preventing diseases. In specific embodiments, the diseases include, but are not limited to, Berger's disease, peripheral arterial disease, coronary artery disease, metabolic syndrome, acute coronary syndrome, aortic valve stenosis, aortic regurgitation, aortic dissection, retinal artery occlusion, cerebrovascular disease, mesenteric ischemia, superior mesenteric artery occlusion, renal artery stenosis, stable / unstable angina pectoris, acute coronary syndrome, heterozygous or homozygous familial hypercholesterolemia, hyperlipoproteinemia, atherosclerosis (e.g., cerebrovascular atherosclerosis), cerebrovascular disease, venous embolism, myocardial infarction, dyslipidemia, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis. In another specific embodiment, the diseases include, but are not limited to, metabolic syndrome, cardiovascular disease, hypertension, type 2 diabetes mellitus, obesity, elevated triglyceride levels, lipodystrophy, liver inflammation, fatty liver disease, elevated liver enzyme-related diseases, non-alcoholic cirrhosis, cardiomyopathy, heart failure, and nephropathy. In another specific embodiment, the diseases include, but are not limited to, senile systemic amyloidosis, generalized familial amyloidosis, familial amyloid polyneuropathy, familial amyloid cardiomyopathy, leptomeningeal / central nervous system amyloidosis, hyperthyroxinemia, Stargardt's disease, diabetic retinopathy, age-related macular degeneration, insulin resistance associated with type 2 diabetes mellitus, and cardiovascular diseases. The present invention specifically relates to the following technical solutions: Technical solution Al. A compound of formula I, or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof: G^A^-     Ab2-Hg2 wherein Gi and G2 are each independently a nucleic acid molecule; Abi and Ab2 are each independently an abasic nucleotide, an inverted nucleotide, -(OCH2CH2)k-, -(CH2CH2O)k-, -O(CH2CH2O)k-, or -(CH2)k-; ni and n2 are each independently 0, 1, 2, or 3, preferably 0 or 1; k is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; X is a linker. Technical solution A2. A compound according to technical solution Al, wherein X is a nucleotide linker, the nucleotide preferably selected from a deoxyribonucleotide, a ribonucleotide, a 2'-deoxy-2'-fluororibonucleotide, a 2'-5' ribonucleotide, or a 2'-5' deoxyribonucleotide. Technical solution A3. A compound according to technical solution A2, wherein X is Nt(dN)m, wherein Nt is selected from a deoxyribonucleotide, a ribonucleotide, a 2'-deoxy-2'-fluororibonucleotide, or a 2'-5' ribonucleotide, dN is each independently selected from dA, dT, dG, or dC, and m is 1, 2, 3, 4, or 5. Technical solution A4. A compound according to technical solution A3, wherein X is selected from (G2p)dAdT, rGdAdT, dCdA, dAdT, dAdCdA, dTdCdA, dAdAdA, dTdTdT, dTdTdTdT, or dTdTdTdTdT. Technical solution A5. A compound according to technical solution Al, wherein X comprises one or more compounds of formula (II): wherein Tg is -S-S-C(Rd)3, -OCH2-S-S-C(Rd)3, a sugar moiety, or a polypeptide; the sugar moiety is preferably a sugar that can be cleaved in the inclusion or lysosome, preferably a five- or six-membered sugar, more preferably a six-membered sugar, more preferably selected from / / -acetylgalactosamine, galactose, / V-acetylghicosamine, glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose; Rd is independently selected from H, D, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, or a GalNAc-containing chain, and is optionally deuterated or fully deuterated; wherein Ra, Rb, and Rc are independently selected from H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, and are optionally deuterated or fully deuterated; wherein Li and L2 are linkers, preferably each independently selected from a bond, -(CH2)P-, -O-(CH2)P-, -(CH2)p-O-, -O-(CH2)P-O-(CH2)q-, -O-(CH2)p-NHCO-, -NHC(O)-, -C(O)NH-, -OC(O)-, -0(0)0-, -S-S-, -NHC(0)0-, -NHC(0)NH-, -00(0)0-, -0C(0)NH-, -0-CH(CH(0H)CH20H)-, -O-CH(CH(NH2)CH2OH)-, -0-CH(CH20H)CH(0H)-, -NH-CH(CH20H)CH(0H)-, -0-CH2CH(0H)CH(0H)-, -O-CH2CH(NH2)CH(OH)-, -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-, -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-, -NHC(0)-CH2-0-CH(CH20H)CH(0H)-, -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-, or -NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-; wherein p and q are each independently 1, 2, 3, 4, 5, or 6; wherein and are connected to Gi or G2 via a bridged linkage; preferably represents connection to Gi via a bridged linkage, and represents connection to G2 via a bridged linkage. Technical solution A6. A compound according to technical solution A5, wherein Tg is -S-S-C(CH3)3. Technical solution A7. A compound according to technical solution A5, wherein Tg is galactose, glucose, N-acetylgalactosamine, or A-acetylglucosamine, preferably galactose. Technical solution A8. A compound according to any one of technical solutions A5 to A7, wherein Ra, Rb, and Rc are each independently selected from H, D, halogen, or C1-6 alkyl, Li and L2 are each independently selected from a bond, -(CH2)P-, -0-(CH2)p-, -(CH2)p-0-, -O-(CH2)p-O-(CH2)q-, or -0-(CH2)p-NHC0-, and p and q are each independently 1, 2, 3, 4, 5, or 6. Technical solution A9. A compound according to technical solution Al, wherein X comprises one or more of the following compounds: Compound No. Structure BL1 OH HO (         Il OH 0 ') 1 BL2 J —z ^0 BL3 H OH 1 OH BL4 y° / * ’"$0 p 0 —z BL5 CO / CO ^0 BL6 |— 6  0 0 Technical solution A10. A compound according to any one of technical solutions Al to A9, wherein Gi and G2 are independently selected from a double-stranded nucleic acid molecule, preferably a dsRNA. Technical solution All. A compound according to technical solution A10, wherein the dsRNA molecule has a sense strand and an antisense strand, each having 14 to 30 nucleotides, wherein the antisense strand comprises a sequence sufficiently complementary to the sense strand and the target mRNA. Technical solution A12. A compound according to technical solution A10 or All, wherein Gi and G2 may target identical or different target mRNAs, preferably different target mRNAs. Technical solution A13. A compound according to any one of technical solutions A10 to A12, wherein Gi and —Ab-, —~— Ab2 — G2 each have a sense strand connected to            nl            112 . Technical solution A14. A compound according to technical solution A13, wherein the 3' end of the antisense strand of each of Gi and G2 is a blunt end or overhang, preferably an overhang, more preferably an overhang of both nucleotides. Technical solution A15. A cell comprising a compound of any one of technical solutions Al to A14. Technical solution A16. A pharmaceutical composition comprising a compound of any one of technical solutions Al to A14, or a cell of technical solution Al5, and optionally a pharmaceutically acceptable carrier or excipient. Technical solution A17. A kit comprising a compound of any one of technical solutions Al to A14, or a cell of technical solution A15. Technical solution Bl. A compound of formula I, or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof: Gi G2 (I) wherein Gi and G2 are each independently a nucleic acid molecule; Abi and Ab2 are each independently an abasic nucleotide, an inverted nucleotide, -(OCthCtDk-, -(CH2CH2O)k-, -O(CH2CH2O)k-, or -(CH2)k-; ni and n2 are each independently 0, 1, 2, or 3, preferably 0 or 1; k is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; X is a linker. Technical solution B2. A compound according to technical solution Bl, wherein X is a nucleotide linker, the nucleotide preferably selected from a deoxyribonucleotide, a ribonucleotide, a 2'-deoxy-2'-fluororibonucleotide, a 2'-5' ribonucleotide, or a 2'-5' deoxyribonucleotide. Technical solution B3. A compound according to technical solution B2, wherein X is Nt(dN)m, wherein Nt is selected from a deoxyribonucleotide, a ribonucleotide, a 2'-deoxy-2'-fluororibonucleotide, or a 2'-5' ribonucleotide, dN is each independently selected from dA, dT, dG, or dC, and m is 1, 2, 3, 4, or 5. Technical solution B4. A compound according to technical solution B3, wherein X is selected from (G2p)dAdT, rGdAdT, dCdA, dAdT, dAdCdA, dTdCdA, dAdAdA, dTdTdT, dTdTdTdT, or dTdTdTdTdT. Technical solution B5. A compound according to technical solution Bl, wherein X comprises one or more compounds of formula (II): wherein Tg is -S-S-C(Rd)3, -OCH2-S-S-C(Rd)3, a sugar moiety, or a polypeptide; the sugar moiety is preferably a sugar that can be cleaved in the inclusion or lysosome, preferably a five- or six-membered sugar, more preferably a six-membered sugar, more preferably selected from A-acetylgalactosamine, galactose, A-acetylglucosamine, glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose; Rd is independently selected from H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, or a GalNAc-containing chain, and is optionally deuterated or fully deuterated; wherein Ra, Rb, and Rc are independently selected from H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, and are optionally deuterated or fully deuterated; wherein Li and L2 are linkers, preferably each independently selected from a bond, -(CH2)P-, -O-(CH2)P-, -(CH2)p-O-, -O-(CH2)P-O-(CH2)q-, -O-(CH2)p-NHCO-, -NHC(O)-, -C(O)NH-, -OC(O)-, -C(O)O-, -S-S-, -NHC(O)O-, -NHC(O)NH-, -OC(O)O-, -OC(O)NH-, -O-CH(CH(OH)CH2OH)-, -O-CH(CH(NH2)CH2OH)-, -O-CH(CH2OH)CH(OH)-, -NH-CH(CH2OH)CH(OH)-, -O-CH2CH(OH)CH(OH)-, -O-CH2CH(NH2)CH(OH)-, -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-, -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-, -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-, or -NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-; wherein p and q are each independently 1, 2, 3, 4, 5, or 6; wherein and are connected to Gi or G2 via a bridged linkage; preferably represents connection to Gi via a bridged linkage, and represents connection to G2 via a bridged linkage. Technical solution B6. A compound according to technical solution B5, wherein Tg is -S-S-C(CH3)3. Technical solution B7. A compound according to technical solution B5, wherein Tg is galactose, glucose, N-acetylgalactosamine, or A-acetylglucosamine, preferably galactose. Technical solution B8. A compound according to any one of technical solutions B5 to B7, wherein Ra, Rb, and Rc are each independently selected from H, D, halogen, or Ci-6 alkyl, Li and L2 are each independently selected from a bond, -(CH2)P-, -O-(CH2)P-, -(CH2)P-O-, -O-(CH2)p-O-(CH2)q-, or -O-(CH2)P-NHCO-, and p and q are each independently 1, 2, 3, 4, 5, or 6. Technical solution B9. A compound according to technical solution Bl, wherein X comprises one or more compounds of formula (III): O Sg—L3X zl5x \ L4 O' (JU) wherein Sg is a sugar moiety, preferably a sugar that can be cleaved in the inclusion or lysosome, preferably a five- or six-membered sugar, more preferably a six-membered sugar, more preferably selected from N-acetylgalactosamine, galactose, / V-acetylghicosamine, glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose; L3 and L4 are linkers, preferably each independently selected from a bond, -(CH2)P-, -O-(CH2)P-, -(CH2)P-O-, -O-(CH2)P-O-(CH2)q-, -O-(CH2)p-NHCO-, -NHC(O)-, -C(O)NH-, -OC(O)-, -C(O)O-, -S-S-, -NHC(O)O-, -NHC(O)NH-, -OC(O)O-, -OC(O)NH-, -O-CH(CH(OH)CH2OH)-, -O-CH(CH(NH2)CH2OH)-, -O-CH(CH2OH)CH(OH)-, -NH-CH(CH2OH)CH(OH)-, -O-CH2CH(OH)CH(OH)-, -O-CH2CH(NH2)CH(OH)-, -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-, -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-, -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-, or -NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-; L5 is a linker, preferably independently selected from a bond, C5-6 cycloalkyl, Ce-io aryl, 5-membered to 6membered heterocyclyl containing 1 to 3 heteroatoms, or 5-membered to 6-membered heteroaryl containing 1 to 3 heteroatoms, wherein the heteroatom is N or 0; wherein and are connected to Gi or G2 via a bridged linkage; preferably represents connection to Gi via a bridged linkage, and represents connection to G2 via a bridged linkage. Technical solution BIO. A compound according to technical solution B9, wherein X comprises one or more compounds of formula (Illa): (Illa) wherein L3, L4, and L5 are as defined above. Technical solution Bll. A compound according to technical solution B9 or BIO, wherein L3 is -O-(CH2)4-, L4 is a bond, and L5 is a bond. Technical solution B12. A compound according to technical solution B9 or BIO, wherein L3 is -O-(CH2)5-, L4 is -OC(O)-, and L5 is Technical solution B13. A compound according to technical solution B9 or BIO, wherein L3 is -O-(CH2)4-, L4 is -C(0)-, and L5 is the fol Technical solution Bl4. A compound according to technical solution Bl, wherein X comprises one or more of comi Compound No. Structure BL1 OH HO (         1    1 ) 0 —z OH BL2 ^S'S z— A 0 / BL3 O          N >o    0 / 0H     II HO (        | J 1 OH BL4 %   0 0 Y 0 T H BL5 0^ O co / co BL6 |—6   0 0 'S 1 ,s BL7 0 HOX° O^ / ^x HO NHAc ^0^ BL8 ? 0 HO( 0 HC>YNHAc T 6 >° 0 BL9 OH H°< 0 HO hC^ 0 0  '—\ Qjw Technical solution Bl5. A compound according to technical solution Bl4, wherein X is BL(dN)m, wherein BL is selected from BL1, BL2, BL3, BL4, BL5, BL6, BL7, BLS, or BL9, preferably BL1, dN is each independently selected from dA, dT, dG, or dC, and m is 1, 2, 3, 4, or 5. : 10 Technical solution B16. A compound according to technical solution B14, wherein X is selected from BL1-dTdTdT orBLl-dCdA. Technical solution Bl7. A compound according to technical solution Bl4, wherein X is (BL)P, wherein BL is selected from BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, or BL9, preferably BL7 or BL8, and p is 1, 2, or 3. Technical solution B18. A compound according to technical solution B17, wherein X is BL7, BL7-BL7-BL7, BL8, BL8-BL8-BL8, BL9, or BL9-BL9-BL9. Technical solution B19. A compound according to any one of technical solutions Bl to B18, wherein Gi and G2 are independently selected from a double-stranded nucleic acid molecule, preferably a dsRNA. Technical solution B20. A compound according to technical solution B19, wherein the dsRNA molecule has a sense strand and an antisense strand, each having 14 to 30 nucleotides, wherein the antisense strand comprises a sequence sufficiently complementary to the sense strand and the target mRNA. Technical solution B21. A compound according to technical solution B19 or B20, wherein Gi and G2 may target identical or different target mRNAs, preferably different target mRNAs. Technical solution B22. A compound according to any one of technical solutions B19 to B21, wherein Gi and —Ab1 —X —— Ab2 — G2 each have a sense strand connected to             11              112 . Technical solution B23. A compound according to technical solution B22, wherein the 3' end of the antisense strand of each of Gi and G2 is a blunt end or overhang, preferably an overhang, more preferably an overhang of both nucleotides. Technical solution B24. A cell comprising a compound of any one of technical solutions Bl to B23. Technical solution B25. A pharmaceutical composition comprising a compound of any one of technical solutions Bl to B23, or a cell of technical solution B24, and optionally a pharmaceutically acceptable carrier or excipient. Technical solution B26. A kit comprising a compound of any one of technical solutions Bl to B23, or a cell of technical solution B24. List of Specific Compounds The compounds of the present invention are numbered and structured in oligonucleotides as follows, wherein represents connection to Gi via a bridged linkage (Si), and represents connection to G2 via a bridged linkage (S2); Compound No. Structure BL1 0H HO (         | OH 0 ^N^°y 1 BL2 ^s's 0 1 BL3 1    X    0-1 OH AXo^N^ 1 “A OU 1 OH BL4 y° / * 3s)        o ""C° o o —z BL5 cn ZA ( A o BL6 |—6   o o BL7 s H0 NHAc BL8 0 nu NHAc           0 BL9 OH                    x ho / „          r\ U N 'x / ° H° HN          0 O '--\ Q» / w BL10 § o HOXvo^o^o^ A H0 NHAc          H 111 'q^\ BL11 HO (° 0                     9 -A H0   NHAc BL12 DH          —°y H\£o. JU    1 HO\Xr-^° NHAc Synthesis Examples The following examples are intended to illustrate the invention and do not limit the scope of the invention. Abbreviation ACN, MeCN Acetonitrile DCI 4,5 -Dicyanoimidazole DCM Dichloromethane DIEA Diisopropylethylamine DMAP 4-Dimethylaminopyridine DMF N,N-Dimethylformamide DMTrCl 4,4'-Dimethoxytrityl chloride EA, EtOAc Ethyl acetate EDCI l-Ethyl-(3 -dimethylaminopropyl) carbodiimide hydrochloride HATU 2-(7-Azabenzotriazol-1 -yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate TEAA Triethylammonium acetate THF Tetrahydrofuran HOBt 1 -Hydroxybenzotriazole MeOH Methanol PDC Pyridinium dichromate PE Petroleum ether PMA Phosphomolybdic acid (for color development) TBAB Tetra butyl ammonium bromide TEA Triethylamine Pd(dppf)Cl2 [1,1 '-Bis(diphenylphosphino)ferrocene]dichloropalladium TBHP tert-Butyl hydroperoxide LiAlH4 Lithium aluminum hydride DIPEA N, N-Diisopropylethylamine DCE Dichloroethane TMSOTf Trimethylsilyl trifluoromethanesulfonate TBDPSC1 tert-Butyldiphenylchlorosilane TBAF Tetrabutylammonium fluoride TLC Thin-layer chromatography LCMS Liquid Chromatography-Mass Spectrometry Example 1: Preparation of Intermediate Compound Example 1.1: Preparation of Compound FEI DMTrCI, Et3N DMAP, DCM 4-Nitrophenyl Et3N, DCM TBAF, THF k DCI, pyridine, DCM FE1 1. Preparation of Intermediate b DMTrCI, Et3N DMAP, DCM H0^X^zBr ------ DMTrO^ / ^ / x^Br a                                        b 5 To a solution of compound a (7.25 mL, 59.86 mmol) in dichloromethane (100 mL), triethylamine (12.11 g, 119.72 mmol), 4-dimethylaminopyridine (1.46 g, 11.97 mmol), and DMTrCI (22.31 g, 65.85 mmol) were sequentially added, and the mixture was stirred at room temperature overnight. After the reaction was complete, the reaction mixture was diluted with dichloromethane, washed with water, and extracted twice with dichloromethane. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, fdtered, and 10 concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0-20% ethyl acetate / petroleum ether) to obtain b (16 g, 34.179 mmol, 57.10%) as a colorless oil. 1H NMR (400 MHz, Chloroform-! / ) 8 7.50 - 7.43 (m, 2H), 7.35 (d, J= 8.9 Hz, 4H), 7.32 - 7.27 (m, 2H), 7.26 - 7.20 (m, 1H), 6.86 (d, J = 8.9 Hz, 4H), 3.82 (s, 6H), 3.42 (t, J= 6.8 Hz, 2H), 3.10 (t, J= 6.4 Hz, 2H), 1.86 (p, J= 6.9 Hz, 2H), 1.71 - 1.61 (m, 2H), 1.57-1.51 (m, 2H). 15 2.   Preparation of Intermediate d c                                   d To a solution of compound c (10.00 g, 46.94 mmol) in super dry tetrahydrofuran (100 mL) under a nitrogen atmosphere, lithium aluminium hydride (LAH, 2.67 g, 70.41 mmol) was added portions, and the mixture was stirred 20 at room temperature for 2 h. After TLC showed that the reaction was complete, the reaction mixture was cooled to 0°C and quenched by the sequential addition of water (2.67 g), 15% sodium hydroxide aqueous solution (2.67 g), and water (8.01 g). The ice-water bath was removed to slowly warm to room temperature, and stirring was continued for 0.5 h. The insoluble matter was removed by filtration through celite. The stock solution was concentrated under reduced pressure, dissolved in ethyl acetate, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain crude product d (white solid, 8.37 g, 38.56 mmol, 82.15%). 3.   Preparation of Intermediate e To a solution of intermediate d (5.00 g, 23.04 mmol) in super dry DMF (50 mL) cooled to 0°C, sodium hydrogen (1.38 g, 34.55 mmol) was added under a nitrogen atmosphere. After stirring at 0°C for 0.5 h, bromide (11.86 g, 25.34 mmol) was added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was then diluted several times with ethyl acetate and washed with water to separate the organic phase. The aqueous phase was extracted twice with ethyl acetate. The organic phases were combined, washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The residue was purified by flash column chromatography (0-30% ethyl acetate / petroleum ether) to obtain intermediate e (2.00 g, 3.31 mmol, 14.37%) as a colorless syrup. 'H NMR (400 MHz, DMSO-t / e) 5 7.49 (d, J= 2.1 Hz, 1H), 7.46 (dd, J= 8.0, 2.2 Hz, 1H), 7.40 - 7.34 (m, 3H), 7.35 - 7.24 (m, 2H), 7.23 (d, J= 8.9 Hz, 4H), 7.21 -7.17 (m, 1H), 6.87 (d, J= 9.0 Hz, 4H), 5.17 (t, J= 5.5 Hz, 1H), 4.48 (d, J= 5.5 Hz, 2H), 4.46 (s, 2H), 3.73 (s, 6H), 3.42 (t, J= 6.3 Hz, 2H), 2.95 (t, J= 6.3 Hz, 2H), 1.53 (dp, J= 21.2, 6.5 Hz, 4H), 1.38 (qd, J= 9.5, 8.7, 5.9 Hz, 2H). 4.   Preparation of Intermediate f B2(pin)2, Pd(dppf)CI2 KOAc, 1,4-dioxane 100°C, 16h . The mixture of intermediate e (3.44 g, 5.69 mmol), bis(pinacolato)diboron (B2(pin)2, 1.74 g, 6.83 mmol), potassium acetate (1.12 g, 11.39 mmol), super dry 1,4-dioxane (30 mL), and Pd(dppf)C12 (0.21 g, 0.28 mmol) was heated to 100°C and stirred overnight under a nitrogen atmosphere until TLC showed the formation of new spots. The volatile matter was concentrated under reduced pressure, and the residue was purified by flash column chromatography to obtain intermediate f (2.97 g, 4.55 mmol, 80.0%) as a yellow syrup. 'H NMR (400 MHz, Chloroform-! / ) 8 7.78 (dd, J= I A, 1.3 Hz, 1H), 7.72 (d, J= 1.2 Hz, 1H), 7.45 - 7.38 (m, 3H), 7.30 (d, J= 8.9 Hz, 4H), 7.29 - 7.22 (m, 2H), 7.21 - 7.16 (m, 1H), 6.81 (d, J= 8.9 Hz, 4H) 4.66 (d, J= 2.9 Hz, 2H), 4.59 (s, 2H), 3.78 (s, 6H), 3.49 (t, J= 6.7 Hz, 2H), 3.02 (t, J= 6.6 Hz, 2H), 1.63 - 1.54 (m, 4H), 1.42 - 1.36 (m, 2H), 1.34 (s, 9H). 5.   Preparation of Intermediate g f NaOH, NH2OH HCI TBHP, MeOH 9 To a solution of intermediate f (2.97 g, 4.55 mmol) in methanol (30 mL), sodium hydroxide (0.73 g, 18.211 mmol) and hydroxylamine hydrochloride (0.95 g, 13.658 mmol) were added, and the reaction mixture was stirred at room temperature for 5 h. Then, tert-butyl hydroperoxide (TBHP, 0.70 g, 5.46 mmol) was added, and the mixture was stirred at room temperature for 1 h until TLC showed that the reaction of the starting material was complete. The volatile matter was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate and washed with water to separate the organic phase. The aqueous phase was extracted twice with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The residue was purified by flash column chromatography (0-30% ethyl acetate / petroleum ether) to obtain intermediate g (2.12 g, 3.91 mmol, 85.87%) as a pale yellow oil. 1H NMR (400 MHz, Chloroform-d) 8 7.44 - 7.41 (m, 2H), 7.27 (d, J= 10.9 Hz, 4H), 7.29 - 7.15 (m, 1H), 6.81 (d, J= 8.9 Hz, 4H), 6.79 (d, J= 2.7 Hz, 1H), 6.73 (dd, J= 8.1, 2.7 Hz, 1H), 5.40 (s, 1H), 4.56 (d, J= 6.3 Hz, 2H), 4.51 (s, 2H), 3.78 (s, 6H), 3.50 (t, . / =6,7 Hz. 2H), 3.13 (t, J= 6.3 Hz, 1H), 3.03 (t, J= 6.5 Hz, 2H), 1.60- 1.52 (m, 4H), 1.42 (ddd, J= 12.3,5.7,3.1 Hz, 2H). 6.   Preparation of Intermediate i OAc g                                                                       ■ To a mixed solvent of water (10 mL) and 1,2-dichloroethane (DCE, 10 mL), intermediate g (2.12 g, 3.91 mmol), sodium hydroxide (0.39 g, 9.77 mmol), and tetrabutylammonium bromide (TBAB, 1.26 g, 3.91 mmol) were added, followed by compound h (2.41 g, 5.86 mmol). The reaction mixture was heated to 80°C and stirred overnight. After TLC showed that the reaction was complete, the reaction mixture was cooled to room temperature and diluted with dichloromethane. The organic phase was separated, washed once with water and once with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (0-40% ethyl acetate / petroleum ether) to obtain compound i (2.12 g, 2.43 mmol, 62.16%) as a white solid. 'H NMR (400 MHz, DMSO-t / 6) 8 7.39 - 7.27 (m, 5H), 7.26 - 7.17 (m, 5H), 6.95 (d, J= 2.6 Hz, 1H), 6.91-6.84 (m, 5H), 5.41 (d, J= 7.8 Hz, 1H), 5.33 (dd, J =3.5, 1.1 Hz, 1H), 5.29 (dd, J= 10.2, 3.5 Hz, 1H), 5.20 (dd, J= 10.2, 7.8 Hz, 1H), 4.98 (t, J= 5.5 Hz, 1H), 4.47 (s, 1H), 4.46 - 4.43 (m, 3H), 4.40 (t, 1H), 4.08 (d, J= 6.3 Hz, 2H), 3.73 (s, 6H), 3.41 (t, J= 6.4 Hz, 2H), 2.94 (t, J= 6.4 Hz, 2H), 2.14 (s, 3H), 2.00 (s, 3H), 1.98 (s, 3H), 1.95 (s, 3H), 1.52 (dq, J= 21.2, 6.7, 6.3 Hz, 4H), 1.37 (qt, J= 6.5, 3.6 Hz, 2H). 7. Preparation of Intermediate j Et3N, THF 4-Nitrophenyl chloroformate Et3N, DCM Intermediate i (2.00 g, 2.29 mmol) was dissolved in dichloromethane (20 mL). The reaction system was cooled to 0°C, and triethylamine (0.70 g, 6.88 mmol) and 4-nitrophenyl chloroformate (0.69 g, 3.44 mmol) were sequentially added and stirred at room temperature for 5 h. After TLC showed that the reaction of the starting material was mostly complete, 2-((tert-butyldimethylsilyl)oxy)-N-methylethan-l-amine (0.87 g, 4.585 mmol) was added and reacted at room temperature overnight until TLC showed that new spots with similar polarity were generated. The reaction mixture was then washed with water and saturated brine, dried over anhydrous sodium sulfate, fdtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (0-40% ethyl acetate / petroleum ether) to obtain intermediate j (1.77 g, 1.63 mmol, 70.99%) as a white amorphous solid. 'H NMR (400 MHz, DMSO-t / 6) 8 7.38 - 7.34 (m, 2H), 7.34 - 7.24 (m, 3H), 7.24 - 7.17 (m, 5H), 6.99 (d, J = 2.5 Hz, 1H), 6.93 - 6.88 (m, 1H), 6.86 (d, J= 8.9 Hz, 4H), 5.46 (d, J= 7.8 Hz, 1H), 5.34 (dd, J= 3.5,1.1 Hz, 1H), 5.30 (dd, J= 10.3, 3.5 Hz, 1H), 5.21 (dd, J= 10.2, 7.8 Hz, 1H), 5.02 (s, 2H), 4.48 (s, 2H), 4.44 - 4.40 (m, 1H), 4.07 (d, J = 6.3 Hz, 2H), 3.72 (s, 6H), 3.62 (dt, J = 19.5, 5.6 Hz, 2H), 3.40 (t, J = 6.5 Hz, 2H), 3.26 (q, J = 5.6 Hz, 2H), 2.93 (t, J= 6.4 Hz, 2H), 2.84 (d, J= 4.5 Hz, 3H), 2.14 (s, 3H), 2.00 (s, 3H), 1.98 (s, 3H), 1.95 (s, 3H), 1.52 (dp, J= 21.6, 6.5 Hz, 4H), 1.41 - 1.32 (m, 2H), 0.80 (d, J= 10.2 Hz, 9H), -0.04 (d, J= 18.5 Hz, 6H). Preparation of Intermediate k o ^x^OTBS OAc TBAF, THF j                                                                                       k To a solution of compound j (1.77 g, 1.63 mmol) in tetrahydrofuran (20 mL), a solution of tetrabutylammonium fluoride (TBAF) in tetrahydrofuran (3.26 mL, 3.26 mmol) was added, and the reaction mixture was stirred at room temperature for 1 h. After TLC showed that the reaction was complete, the solvent was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate and washed once with water to separate the organic phase. The aqueous phase was extracted twice with ethyl acetate. The organic phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (0-100% ethyl acetate / petroleum ether) to obtain intermediate k (1.32 g, 1.36 mmol, 83.32%). 'H NMR (400 MHz, DMSO-t / 6) 5 7.38 - 7.33 (m, 2H), 7.32 - 7.26 (m, 3H), 7.25 -7.19 (m, 5H), 7.00 - 6.98 (m, 1H), 6.92 (dd, J= 8.3, 2.0 Hz, 1H), 6.87 (d, J= 8.9 Hz, 4H), 5.46 (d, J= 7.9 Hz, 1H), 5.34 (dd, J =3.6, 1.0 Hz, 1H), 5.29 (dd, J= 10.3,3.5 Hz, 1H), 5.20 (dd, J= 10.3, 7.8 Hz, 1H), 5.02 (s, 2H), 4.68 (td, J= 10.7, 5.2 Hz, 1H), 4.48 (s, 2H), 4.42 (t, J= 6.4 Hz, 1H), 4.08 (d, J= 6.3 Hz, 2H), 3.72 (s, 6H), 3.49-3.44 (m, 2H), 3.41 (t, J= 6.4 Hz, 2H), 3.23 (t, J= 6.0 Hz, 2H), 2.94 (t, J= 6.4 Hz, 2H), 2.85 (s, 3H), 2.14 (s, 3H), 2.01 (s, 3H), 1.98 (s, 3H), 1.95 (s, 3H), 1.52 (ddd, J= 29.0, 13.6, 6.4 Hz, 4H), 1.37 (ddd, J= 11.3, 7.7, 4.0 Hz, 2H). To a solution of compound k (0.43 g, 0.442 mmol) in dichloromethane (5 mL), pyridine (0.17 g, 2.2 mmol), 2-cyanoethyl tetraisopropylphosphorodiamidite (0.27 g, 0.88 mmol), and 4,5-dicyanoimidazole (DCI, 0.07 g, 0.57 mmol) were added at room temperature. The reaction mixture was stirred overnight. After TLC (PE / EA = 1 / 1) showed that the reaction was complete, the reaction mixture was cooled to 0°C. Then, IN NaOH aqueous solution (20 mL) was added and stirred at 0°C for 0.5 h to separate the organic phase. The aqueous phase was extracted twice with dichloromethane. The organic phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, fdtered, and concentrated. The residue was purified by flash column chromatography (eluent: 042% ethyl acetate / petroleum ether containing 1% EtsN). The obtained crude product was further purified by reversed-phase flash column chromatography (0-98% acetonitrile / water) to obtain FEI (300 mg, 0.256 mmol, 57.87%) as a colorless oil. 'H NMR (400 MHz, Chloroform-t / ) 8 7.44 - 7.40 (m, 2H), 7.31 (d, J= 8.9 Hz, 4H), 7.32 - 7.22 (m, 3H), 7.22 - 7.16 (m, 1H), 6.91 (dd, J= 8.4, 2.6 Hz, 1H), 6.81 (d, J= 8.9 Hz, 4H), 5.51 - 5.43 (m, 2H), 5.12 (s, 2H), 5.10 (dd, J= 10.4, 3.4 Hz, 1H), 5.05 (d, J= 7.9 Hz, 1H), 4.52 (s, 2H), 4.22-4.15 (m, 2H), 4.05 (t, J = 6.7 Hz, 1H), 3.78 (s, 6H), 3.77 - 3.70 (m, 2H), 3.63 - 3.53 (m, 2H), 3.47 (t, J= 6.5 Hz, 4H), 3.04 (t, J= 6.6 Hz, 2H), 2.97 (d, J= 7.5 Hz, 3H), 2.58 (q, J= 6.7 Hz, 2H), 2.18 (s, 3H), 2.04 (s, 6H), 2.01 (s, 3H), 1.67 - 1.54 (m, 6H), 1.47 - 1.36 (m, 2H), 1.34 - 1.28 (m, 1H), 1.190 - 1.10 (m, 12H). 31P NMR (400 MHz, Chloroform-^ / ) 8 148.12, 148.03. DMTrCI Py, THF DCI, DCM ODMTr 1 Preparation of Intermediate 2 F 1 Na2S DMF Compound 1 (25.0 g, 117.8 mmol) was dissolved in DMF (150 mL), and then Na2S (9.20 g, 117.82 mmol) was added at 25 °C and allowed to dissolve slowly. The reaction was allowed to proceed at 25 °C for 13 h until TLC (petroleum etherethyl acetate = 5:1) showed that the starting material disappeared and new spots were formed. The reaction mixture was then adjusted to pH 4-5 with 2N hydrochloric acid. The aqueous phase was extracted twice with ethyl acetate (200 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and spin-dried to obtain compound 2 (35.0 g, 154.696 mmol) as a yellow oil. 'H NMR (400 MHz, CD3OD) d 7.25-7.90 (m, 3H), 3.80-3.92 (m, 6H) 2 Preparation of Intermediate 3 SH                        SH 2                               3 Compound 2 (35.0 g, 155 mmol) was dissolved in THF (100 mL). After cooling to 0°C, HAIH4 (309 mL, 773 mmol) was added dropwise to the mixture at 0°C. After completion of the dropwise addition, the mixture was stirred at 25°C for 12 h until TLC (DCM / MeOH = 10 / 1) showed that the starting material was completely consumed and new spots were formed. The reaction mixture was then carefully and slowly added to saturated ammonium chloride aqueous solution (1000 mL) at 0°C to quench excess HAIH4 while maintaining the temperature at 0°C. The mixture was extracted three times with ethyl acetate (1000 mL x 3), and the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain compound 3 (19.2 g, 112 mmol,) as a yellow oil.1H NMR (400 MHz, CD3OD) d 6.89-7.41 (m, 3H), 4.60-4.72 (m, 4H) 3 Preparation of Intermediate 4 Compound 3 (10.0 g, 58.7 mmol) was dissolved in absolute ethanol (100 mL). tert-Butyl mercaptan (tBuSH, 59.6 mL, 528 mmol) was added, and a solution of L (9.58 g, 29.4 mmol) in ethanol (100 mL) was added dropwise at 0°C for reaction at 25°C for 2 h until TLC (PE / EA = 1:1) showed that the starting material disappeared and new spots were formed. The mixture was then adjusted to pH 7 with saturated sodium bicarbonate and extracted with ethyl acetate (30.0 mL x 3). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude compound. The crude compound was purified by column chromatography (PE / EA = 1 / 0 to 1 / 1) to obtain compound 4 (5.0 g, 19.4 mmol) as a yellow oil. 1H NMR (400 MHz, CD3OD) d 7.63 (d, J = 2.0 Hz, 1H), 7.47 (dd, J = 2.0, 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 4.70 (s, 2H), 4.65 (s, 2H), 1.29 (s, 9H) 4 Preparation of Intermediate 5 5 Compound 4 (4.30 g, 16.6 mmol) was dissolved in THF (80.0 mL) at 25°C. Pyridine (Py, 2.00 mL, 25.0 mmol) and DMTrCl (5.64 g, 16.0 mmol) were sequentially added, and the mixture was stirred at 25°C for 12 h until TLC (PE / EA = 3 / 1) showed that new spots were formed. Ethyl acetate (200 mL) was added thereto, and the mixture was washed with saturated sodium bicarbonate solution (50 mL x 3) and saturated brine (50 mL x 3) in sequence. The obtained organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (PE / EA = 1 / 0 to 3 / 1) to obtain compound 5 (1.80 g, 3.21 mmol) as a yellow oil. 'H NMR (400 MHz, CD3OD) d 7.64 (d, J = 1.6 Hz, 1H), 7.447.49 (m, 3H), 7.38-7.43 (m, 1H), 7.33-7.38 (m, 4H), 7.29 (t, J = 7.2 Hz, 2H), 7.18-7.24 (m, 1H), 6.82-6.91 (m, 4H), 4.45 (s, 2H), 4.15 (s, 2H), 3.78 (s, 6H), 1.31 (s, 9H) 5 Preparation of Compound FE2 DCI, DCM ODMTr FE2 Compound 5 (2.00 g, 3.56 mmol) was dissolved in DCM (30.0 mL) at 25°C. DCI (0.42 g, 3.56 mmol) and compound 6 (1.61 g, 5.35 mmol) were sequentially added, and the mixture was stirred at 25°C for 2 h until TLC (T1 :PE / EA = 3 / 1) showed that the starting material was completely consumed and TLC (T2:PE / EA = 10 / 1) showed that new spots with less polarity were formed. The reaction mixture was concentrated directly under reduced pressure to obtain a crude yellow liquid. The crude product was purified by column chromatography (PE (0.02% TEA) / EA = 1 / 0 to 100 / 2) to obtain compound FE2 (2.40 g, 3.15 mmol) as a colorless oil. ’H NMR (400 MHz, CDCL) d 7.61 (s, 1H), 7.45-7.54 (m, 4H), 7.38 (d, J= 8.8 Hz, 4H), 7.27-7.33 (m, 2H), 7.19-7.26 (m, 1H), 6.81-6.88 (m, 4H), 4.39-4.66 (m, 2H), 4.10-4.21 (m, 2H), 3.76-3.81 (m, 6H), 3.68-3.75 (m, 2H), 3.50-3.65 (m, 2H), 2.47-2.55 (m, 2H), 1.33 (s, 9H), 1.18 (d, J= 6.8 Hz, 6H), 1.09 (d, J= 6.8 Hz, 6H); 31PNMR(400 MHz, CDCL) d 148.395. Example 1.3: Preparation of Compound FE3 1-3 TosCI, TEA                            nBu4NHSO4, KOH DMTrO^^^OH ----------► DMTrO^^^OTos ---------- ,          DCM, 0 ~ 25 °C              „              2-MeTHF, 80 °C DMTrO DCI, DCM 0 - 20 °C FE3 1 Synthesis of Compound 2 TosCI, TEA DMTrO^^^^OH -----------► DMTrO'^^^OTos „           DCM, 0 - 25 °C              , 1                                               2 Compound 1 (3.50 g, 9.24 mmol, 1.00 eq) was dissolved in DCM (35.0 mL). Triethylamine (1.87 g, 18.4 mmol, 2.00 eq) was first added, and p-toluenesulfonyl chloride (TosCI, 2.82 g, 14.7 mmol, 1.60 eq) was added after the mixture was cooled to 0°C. The mixture was stirred at 25°C for 16 h After LCMS showed that the substrate reaction was complete, the reaction mixture was neutralized with saturated sodium bicarbonate (50.0 mL) and extracted twice with ethyl acetate (100 mL). The organic phases were combined, washed with saturated brine (50.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography to obtain compound 2 (4.00 g, 7.31 mmol, 79.0%) as a colorless oil. 1H NMR: 400 MHz DMSO 8 7.73-7.71 (d, J= 8.0 Hz, 2H), 7.45-7.43 (d, J= 8.0 Hz, 2H), 7.30-7.12 (m, 9H), 6.87-6.84 (d, J= 12 Hz, 4H), 4.13-4.10 (t, J= 12 Hz, 2H), 3.73 (s, 6H), 2.95-2.90 (t, J= 12 Hz, 2H), 2.38 (s, 3H), 1.98 (s, 3H), 1.84-1.78 (m, 2H). 2  Synthesis of Compound 3 HOZ, HO’ nBu4NHSO4, KOH 2-MeTHF, 80 °C 3 Compound 1-3 (2.86 g, 15.0 mmol, 4.00 eq) and nBu4NHSO4 (0.25 g, 0.751 mmol, 0.20 eq) were dissolved in 2-MeTHF (16.0 mL), and 5 M potassium hydroxide (1.47 g, 26.2 mmol, 7.00 eq) was added at 25°C. After the reaction mixture was clear, compound 2 (2.00 g, 3.75 mmol, 1.00 eq) was dissolved in 2-MeTHF (16.0 mL), which was then added to the above reaction mixture, and the mixture was stirred in an oil bath at 80°C for 16 h. After LCMS showed that the reaction was complete, the reaction mixture was extracted twice with 2-MeTHF (20.0 mL). The organic phases were combined, washed with saturated brine (20.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified by fractionation to obtain oil-free compound 3 (650 mg, 1.26 mmol, 18.1%). 1H NMR: 400 MHz DMSO 8 7.37-7.19 (m, 9H), 6.89-6.87 (m, 4H), 5.17-5.16 (d, J= 4.0 Hz, 1H), 3.73 (s, 6H), 3.68-3.60 (m, 2H), 3.183.10 (m, 5H), 2.75-2.69 (m, 1H), 2.61-2.55 (m, 1H), 1.80-1.74 (m, 2H). 3  Synthesis of Compound FE3 3                                                FE3 Compound 3 (600 mg, 1.17 mmol, 1.00 eq) was dissolved in dichloromethane (6.00 mL). Compound A (0.55 mL, 1.75 mmol, 1.50 eq) was added, and 4,5-dicyanoimidazole (152 mg, 1.28 mmol, 1.10 eq) was added after cooling in an ice-water bath, and the mixture was stirred at 20°C for 2 h. After LCMS showed that the reaction was complete, the reaction mixture was washed 5 times with saturated sodium bicarbonate (5.00 mL) and extracted with dichloromethane (20.0 mL). The organic phase was washed with saturated brine (20.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography to obtain FE3 (450 mg, 0.60 mmol) as a colorless oil. Example 1.4: Preparation of Compound FE4 Compound FE4 can be synthesized according to the method disclosed in PCT Publication No. WO2018136620, see, for example, compound 106 in Example 12. Example 1.5: Preparation of Compound FE5 Ch ODMTr 2) HN^'OTBDPSg 1) PCM,TEA 2 N°2 ODMTr TBAF.THF Compound 1 can be synthesized according to the method disclosed in PCT Publication No. WO2018136620, see, for example, compound 105 in Example 12. To a solution of compound 1 (650 mg, 0.82 mmol) in dichloromethane (7 mL), triethylamine (0.36 mL, 2.57 mmol) and compound 2 (258 mg, 1.28 mmol) were added at 0°C. After stirring at room temperature for 2 h, compound 3 (557.19 mg, 1.712 mmol) was added. After stirring at room temperature overnight, water and ethyl acetate were added to the reaction mixture. The aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with saturated sodium bicarbonate and saturated brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography (eluent: petroleum ether and ethyl acetate) to obtain compound 4 (0.91 g, yield: 90.0%). m / z:ES+ [M+H]+ 1170.37 2. Preparation of Compound 5 ODMTr OTBDPS TBAF.THF ODMTr To a solution of compound 4 (910 mg, 0.78 mmol) in tetrahydrofuran (9 mL), tetrabutylammonium fluoride (TBAF, 0.93 mL, 0.93 mmol) was added at 0°C, and the mixture was stirred at room temperature for 2 h. Water was added, and the reaction mixture was extracted with EA. The organic phases were combined, washed with saturated ammonium chloride and saturated brine, dried over sodium sulfate, fdtered, and concentrated. The obtained crude product was purified by silica gel column chromatography (eluent: dichloromethane and methanol) to obtain compound 5 (0.7 g, yield: 97%). m / z: ES+ [M+H]+ 932.40 3. Preparation of Compound FES To a solution of compound 5 (700 mg, 0.76 mmol) in anhydrous dichloromethane (7 mL), pyridine (0.3 mL, 3.78 mmol), compound 6 (342 mg, 1.14 mmol), and 4,5-dicyanoimidazole (DCI, 107 mg, 0.91 mmol) were added at 0°C, and the reaction was allowed to proceed at room temperature for 1 h. After the reaction was complete, saturated sodium bicarbonate solution was added at 0°C and stirred for 10 min for extraction and liquid separation. The organic phases were combined, washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The obtained crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 40:60,1% triethylamine) to obtain compound FE5 (560 mg, yield: 65%). m / z: ES+ [M+H]+ 1132.27 1H NMR (400 MHz, Chloroform-d) 8 7.95 - 7.89 (m, 2H), 7.88 - 7.82 (m, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.53 - 7.47 (m, 1H), 7.41 (t, J = 7.7 Hz, 2H), 7.36 - 7.29 (m, 4H), 7.25 - 7.07 (m, 7H), 6.73 - 6.60 (m, 4H), 5.97 (d, J = 3.4 Hz, 1H), 5.84 - 5.60 (m, 2H), 4.78 (dt, J = 8.5, 2.4 Hz, 1H), 4.47 (s, 1H), 4.25 - 3.90 (m, 6H), 3.88 - 3.71 (m, 2H), 3.69 (s, 3H), 3.67 (s, 3H), 3.64 - 3.43 (m, 8H), 3.40 (dd, J = 8.9, 5.6 Hz, 1H), 3.22 (t, J = 8.6 Hz, 1H), 2.61 (td, J = 6.3, 4.2 Hz, 2H), 1.86 (s, 3H), 1.66- 1.55 (m, 4H), 1.47- 1.36 (m, 2H), 1.20-1.11 (m, 12H). Example 1.6: Preparation of Compound FE6 OBn                                  OBn OH 2                                             3 ODMTr 1. Synthesis of Compound 2 Compound 1 (10.00 g, 26.06 mmol) was dissolved in DCM (100 mL), and DIPEA (13.84 mL g, 78.17 mmol) and HATU (11.89 g, 31.27 mmol) were sequentially added under a nitrogen atmosphere in an ice bath. The resulting reaction mixture was stirred at room temperature overnight. A large amount of water was added, and the mixture was extracted with DCM, dried over anhydrous Na2SO4, and evaporated under reduced pressure to remove the organic solvent. The residue was purified by silica gel column chromatography to obtain compound 2 (12.5 g, 23.88 mmol, 91%). 2. Synthesis of Compound 3 OAc                                  OAc OBn                                  OBn 2                                               3 Compound 2 (12.5 g, 23.88 mmol) was dissolved in DCE (125 mL), and TMSOTf (5.19 mL, 28.65 mmol) was added dropwise under an argon atmosphere. The reaction was allowed to proceed at room temperature overnight. The reaction mixture was slowly poured into a saturated sodium bicarbonate aqueous solution (200 mL), stirred for 0.5 h, and extracted with DCM. The organic phases were combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the organic solvent. The obtained crude compound 3 (10.2 g) was directly used in the next reaction without further purification. 3. Synthesis of Compound 3b TBDPSCI /   \(R)            _______________ hn^Z’OH           * Imidazole 3a           DCM 47 H^^OTBDPS 3b Compound 3a (5.00 g, 57.40 mmol) and imidazole (5.85 g, 86.10 mmol) were dissolved in DCM (50 mL), and TBDPSC1 (19.15 g, 68.85 mmol) was added dropwise under a nitrogen atmosphere in an ice bath. The reaction was allowed to proceed at room temperature for 3 h. The reaction mixture was washed with saturated sodium bicarbonate and extracted with DCM. The organic phases were combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the organic solvent. The residue was purified by silica gel column chromatography (MeOH / DCM system) to obtain compound 3b (10.7 g, 62%) as a colorless liquid. 4. Synthesis of Compound 3c Compound 3b (10.7 g, 32.87 mmol) and cyclocaprolactone (1.65 g, 16.43 mmol) were dissolved in triethylamine (100 mL) and reacted at 90°C overnight. The reaction mixture was concentrated and purified by silica gel column chromatography to obtain compound 3c (5.10 g, 36.5%). 5. Synthesis of Compound 4 TMSOTf,DCM,r.t Compound 3 (10.2 g, 22.01 mmol) and compound 3c (4.68 g, 11.00 mmol) were dissolved in 100 mL of DCM. TMSOTf (0.8 mL, 4.4 mmol) was added under a nitrogen atmosphere, and the reaction was allowed to proceed at room temperature overnight. Then, 100 mL of saturated sodium bicarbonate was added and the mixture was extracted with dichloromethane. The organic phases were combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the organic solvent. The residue was purified by silica gel column chromatography to obtain compound 4 (6.1 g, 62%). 6. Synthesis of Compound 5 10% HCQQH in MeOH Pd(OH)2 / C 5 Compound 4 (6.1 g, 8.87 mmol) was dissolved in methanol (60 mL) containing 10% formic acid; 6 g of Pd(OH)2 / C was added, and the reaction was allowed to proceed at room temperature under an argon atmosphere overnight. A sufficient amount of saturated sodium bicarbonate aqueous solution was added, and the mixture was extracted with dichloromethane. The organic phases were combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the organic solvent. The residue was purified by silica gel column chromatography to obtain compound 5 (3.50 g, 63.85%). 7. Synthesis of Compound 6 OH 5 6 Compound 5 (3.50 g, 4.38 mmol) was dissolved in 35 mL of anhydrous pyridine. DMTrCl (2.97 g, 8.76 mmol) was added under a nitrogen atmosphere, and the reaction was allowed to proceed at room temperature overnight. After the reaction was complete, the mixture was evaporated under reduced pressure to remove most of the pyridine. Water (100 mL) was added, and the mixture was extracted with dichloromethane. The organic phases were combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the organic solvent. The residue was purified by silica gel column chromatography (50%-100% EA / PE) to obtain compound 6 (3.1 g, 64.2%). Compound 6 (3.1 g, 2.81 mmol) and TBAF (4.22 mL in 1 M THF) were dissolved in tetrahydrofuran (30 mL). The mixture was allowed to react at room temperature for 3 h, and then evaporated under reduced pressure to remove the organic solvent. Water (100 mL) was added, and the mixture was extracted with dichloromethane. The organic phases were combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the organic solvent. The residue was purified by silica gel column chromatography (l%-5% MeOH / DCM) to obtain compound 7 (2.1 g, 86.5%). N(i-Pr)2 (i-Pr)2N'%^^™) DCI,Py,DCM ODMTr FE6 Compound 7 (1.0 g, 1.16 mmol) was dissolved in anhydrous dichloromethane (10 mL). Anhydrous pyridine (0.46 mL, 5.79 mmol), reagent A (0.55 mL, 1.74 mmol), and dicyanoimidazole (0.10 g, 0.8 mmol) were sequentially added under a nitrogen atmosphere. The mixture was allowed to react at room temperature for 3 h. Then, water (50 mL) was added, and the mixture was extracted dichloromethane (3 x 20 mL). The organic phases were combined, washed 5 times with saturated sodium bicarbonate, then washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the organic solvent. The residue was purified by silica gel column chromatography (1 %—75% EA / PE (1% TEA)) to obtain compound FE6 (0.6 g, 48.7%). 1H NMR (400 MHz, Chloroform-d) 8 7.45 - 7.36 (m, 2H), 7.29 (dd, J = 8.8, 2.5 Hz, 5H), 7.26 (d, J = 2.2 Hz, 1H), 7.24 - 7.15 (m, 1H), 6.88 - 6.76 (m, 4H), 6.29 (t, J = 8.3 Hz, 1H), 6.10 (dd, J = 18.8, 8.6 Hz, 1H), 5.34 (d, J = 3.4 Hz, 1H), 5.23 - 5.09 (m, 1H), 4.61 - 4.44 (m, 2H), 4.23 - 3.95 (m, 3H), 3.66 - 3.39 (m, 7H), 3.18 - 3.03 (m, 2H), 2.68 - 2.52 (m, 2H), 2.35 - 2.18 (m, 4H), 2.15 (d, J = 1.4 Hz, 3H), 2.05 (s, 3H), 1.93 (s, 3H), 1.87 (q, J = 7.2 Hz, 2H), 1.73 (s, 3H), 1.67- 1.50 (m, 3H), 1.21 - 1.12 (m, 12H). Example 1.7 Synthesis of Compound FE7 NHAc TBAB, 1N NaOH, DCM DCM H p-NO2PhOCOCI, TEA TEA.{HF)3 TEA.THF NHAc (i-Pr)2N?,O^CN N(i-Pr)2 DCI Py DCM NHAc FE7 TBAB, 1N NaOH, DCM NHAc NHAc Compound 1 (1.47 g, 2.71 mmol, i.e. compound g of Example 1.1) and TBAB (810 mg) were dissolved in 13.5 mL of DCM. Then, 1 N NaOH (6.75 mL) was added under an ice bath, followed by the dropwise addition of a solution of GalNAc-Cl in DCM (900 mg, 2 mL DCM). The reaction mixture was stirred at room temperature for 2 h, then quenched with saturated ammonium chloride, extracted with DCM, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the organic solvent. The residue was purified by silica gel column chromatography (30%-100% DCM / EA) to obtain compound 5 (750 mg, 0.86 mmol, 35%). ’H NMR (400 MHz, DMSO-J6) 5 7.94 (d, J= 9.1 Hz, 1H), 7.40 - 7.33 (m, 2H), 7.30 (td, J= 8.2, 2.5 Hz, 3H), 7.25-7.18 (m, 5H), 6.94 (d, J=2.6Hz, 1H), 6.92- 6.83 (m, 5H), 5.30 (d, J=3.4 Hz, 1H), 5.17 (d, J = 8.5 Hz, 1H), 5.10 (dd, J= 11.2, 3.4 Hz, 1H), 4.96 (t, J= 5.5 Hz, 1H), 4.52-4.41 (m, 4H), 4.29 - 4.22 (m, 1H), 4.16 (dt, J = 11.3, 8.8 Hz, 1H), 4.04 (dd,J= 12.6, 6.7 Hz, 2H),3.73 (s, 6H), 3.40 (d, J= 12.8 Hz, 2H), 2.95 (t,J=6.4Hz, 2H), 2.13 (s, 3H), 1.98 (d, J= 3.2 Hz, 3H), 1.93 (s, 3H), 1.78 (s, 3H), 1.53 (dp, J= 21.4, 6.6 Hz, 4H), 1.37 (td, J= 8.5, 4.4 Hz, 2H), 1.28 - 1.15 (m, 2H). 2. Synthesis of Compound 6 -N^0TBS H a DCM O Anxx^OTBS I NHAc 6 Compound 5 (750 mg, 0.86 mmol) was dissolved in anhydrous DCM (10 mL). TEA (261 mg, 2.58 mmol) and p-nitrobenzyl-chloroformate (260.1 mg, 1.29 mmol) were added dropwise under a nitrogen atmosphere in an ice bath and stirred at room temperature for 3 h. After TLC and LCMS showed the complete formation of the intermediate, compound a (326 mg, 1.72 mmol) was added and reacted overnight. After the reaction was complete, the reaction mixture was washed with water, extracted with DCM, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography to obtain compound 6 (570 mg, 0.524 mmol, 60.95%). ’H NMR (400 MHz, DMSO-tL) 5 7.93 (d, J= 9.1 Hz, 1H), 7.38 - 7.18 (m, 10H), 6.98 (d, J= 2.5 Hz, 1H), 6.93 -6.79 (m, 5H), 5.32 - 5.28 (m, 1H), 5.21 (d, J =8.5 Hz, 1H), 5.11 (dd, J = 11.2, 3.4 Hz, 1H), 5.01 (s, 2H), 4.47 (s, 2H), 4.27 (t, J= 6.3 Hz, 1H), 4.21 - 4.11 (m, 1H), 4.06 (d, J= 6.2 Hz, 2H), 3.72 (s, 6H), 3.68 - 3.57 (m, 2H), 3.40 (d, J= 12.9 Hz, 2H), 3.26 (d, J= 5.5 Hz, 2H), 2.94 (t, J= 6.4 Hz, 2H), 2.84 (d, J= 2.5 Hz, 3H), 2.13 (s, 3H), 1.97 (s, 3H), 1.93 (s, 3H), 1.77 (s, 3H), 1.52 (dp, J = 21.6, 6.7 Hz, 4H), 1.37 (q, J =8.4 Hz, 2H), 1.25 (d,J = 9.1 Hz, 1H), 0.81 (d, J = 8.3 Hz, 9H), -0.05 (s, 6H). Synthesis of Compound 7 6                                                                7 Compound 6 (570 mg, 0.52 mmol) was dissolved in THF (5 mL). EhN (265 mg, 2.62 mmol) and TEA.(HF)3 (254 mg, 1.57 mmol) were added and reacted at room temperature overnight. After the reaction was complete, water was added, and the mixture was extracted with DCM, dried over anhydrous sodium sulfate, fdtered, and concentrated to dryness. The residue was purified by silica gel column chromatography to obtain compound 7 (470 mg, 0.48 mmol, 92%). 4. Synthesis of Compound FE7 DMTrO^^^.O.     Q     0'^        DMTrO^^^,O.     Q OAc                                  N(l Pr)2                   OAc "AG JU I       cs„2n. ■ ("lLo oJU 1 AcOX>J\^O                                     AcOXUr-^°                [   | NHAc                           py                    NHAc DCM 7                                                                 FE7 ■^CN To a solution of compound 7 (470 mg, 0.483 mmol) in dichloromethane (5 mL), pyridine (191.03 mg, 2.415 mmol), 2-cyanoethyltetraisopropylphosphorodiamidite (218.37 mg, 0.725 mmol), and 4,5-dicyanoimidazole (39.93 mg, 0.338 mmol) were added under a nitrogen atmosphere, and the mixture was allowed to react at room temperature. After TLC showed that the reaction was complete, saturated sodium bicarbonate aqueous solution was added and stirred at 0°C for 0.5 h to separate the organic phase. The aqueous phase was extracted twice with dichloromethane. The organic phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, fdtered, and concentrated. The residue was purified by flash column chromatography (eluent: 0-42% ethyl acetate / petroleum ether containing 1% EtjN) to obtain compound FE7 (330 mg, 0.28 mmol, 58.2%). ’H NMR (400 MHz, DMSO-J6) 8 7.93 (d, J = 9.2 Hz, 1H), 7.41 - 7.34 (m, 2H), 7.33 - 7.25 (m, 3H), 7.25 -7.15 (m, 5H), 6.98 (d,J=2.6Hz, 1H), 6.94-6.81 (m, 5H), 5.30 (d, J= 4.2 Hz, 1H),5.21 (d,J=8.4Hz, 1H), 5.11 (dd, J= 11.2, 3.4 Hz, 1H), 5.02 (s, 2H), 4.48 (s, 2H), 4.27 (t, J= 6.4 Hz, 1H), 4.06 (d, J= 6.3 Hz, 2H), 3.73 (s, 6H), 3.70 - 3.45 (m, 6H), 3.39 (d, J= 12.0 Hz, 4H), 2.94 (t, J= 6.4 Hz, 2H), 2.86 (s, 3H), 2.71 (q, J= 6.2, 5.5 Hz, 2H), 2.13 (s, 3H), 1.97 (s, 3H), 1.93 (s, 3H), 1.77 (s, 3H), 1.61 - 1.44 (m, 4H), 1.37 (td, J= 8.3, 3.9 Hz, 2H), 1.14 - 1.01 (m, 12H). 31PNMR (162 MHz, DMSO-J6) 8 146.92. Example 1.8 Synthesis of Compound FE8 NC—\ DCI,Py,DCM FE8 NaOMe MeOH Compound 1 (7.5 g, 12.2 mmol, for synthesis, see, for example, PCT Publication No. WO2023143571) was dissolved in 150 mL of methanol. A solution of sodium methoxide in methanol (0.5 M, 9.8 mL, 4.9 mmol) was added under a nitrogen atmosphere and stirred at room temperature overnight. After the reaction was complete, the 10 mixture was adjusted to pH 7 with acetic acid and concentrated under reduced pressure. The residue was dissolved in dichloromethane containing a small amount of methanol, and a 50 / 50 solution of diethyl ether in hexane (500 mL) was added dropwise. The product was precipitated and fdtered to obtain compound 2 (4.0 g, 67%). 2.  Synthesis of Compound 3 OH                               DMTrCI         ODMTr 2                                                                3 To a solution of compound 2 (5.0 g, 10.28 mmol) in anhydrous pyridine (50 mL), triethylamine (1.04 g, 10.28 mmol), DMAP (0.12 g, 1.03 mmol), and DMTrCI (3.38 g, 11.3 mmol) were added and stirred at room temperature overnight. After the reaction was complete, the reaction mixture was quenched with methanol. The residue was 15 spin-dried, dissolved in dichloromethane, washed with saturated sodium bicarbonate and saturated brine, dried over sodium sulfate, fdtered, and spin-dried to obtain a crude product, which was directly used for the next reaction. 3. Synthesis of Compound 4 ODMTr NHCbz 3 DMAP Bz2O To a solution of compound 3 in anhydrous pyridine (100 mL), DMAP (1.24 g, 10.14 mmol) and benzoic anhydride (6.88 g, 30.42 mmol) were added at 0°C, and the mixture was stirred at room temperature overnight. After the reaction was complete, the reaction mixture was quenched with water and spin-dried. The residue dissolved in ethyl acetate, washed with saturated sodium bicarbonate and saturated brine, dried over sodium sulfate, fdtered, and spin-dried. The obtained residue was purified by column chromatographed to obtain compound 4 (4.8 g, yield 47% in two steps). 4. Synthesis of Compound 5 ODMTr ODMTr 5 Compound 4 (4.8 g) was dissolved in THF (50 mL). Palladium on carbon (Pd / C, 1.0 g) was added, and the mixture was allowed to react under a hydrogen atmosphere overnight. After the reaction was complete, the mixture was filtered through celite and concentrated to obtain compound 5 (3.8 g, 91%). 5. Synthesis of Compound 6 o DMF 5 6 To a solution of compound 5 (3.8 g, 4.40 mmol) in DMF (40 mL), DIPEA (1.71 g, 13.2 mmol) and HATU (1.84 g, 4.84 mmol) were added, and the mixture was allowed to react at room temperature for 3 h. After the reaction was complete, a large amount of water was added, and the mixture was extracted with EA. The product was purified by silica gel column chromatography to obtain compound 6 (2.2 g, 51%). 6. Synthesis of Compound FE8 NC—\ To a solution of compound 6 (1.5 g, 1.52 mmol) in anhydrous dichloromethane (15 mL), DIPEA (590 mg, 4.55 mmol) and compound 2 (540 mg, 2.28 mmol) were added at 0°C, and the mixture was allowed to react at room temperature for 1 h. After the reaction was complete, saturated sodium bicarbonate solution was added at 0°C and stirred for 10 min for extraction and liquid separation. The organic phases were combined, washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (DCM: EA = 50:50, 0.1% TEA) to obtain compound FE8 (530 mg, yield: 29%). m / z: ES+ [M+H]+ 1189.39 1H NMR (400 MHz, DMSO-tL) 8 7.97 (d, J= 9.3 Hz, 1H), 7.79 - 7.68 (m, 6H), 7.62 (t, J= 7.4 Hz, 1H), 7.54 (t, J= 7.6 Hz, 2H), 7.43 (t, J= 7.6 Hz, 2H), 7.32 (d, J= 7.1 Hz, 2H), 7.17 (ddd, J= 18.6, 13.0, 7.5 Hz, 7H), 6.776.63 (m, 4H), 5.87 (d, J= 3.4 Hz, 1H), 5.38 (dd, J= 11.1, 3.3 Hz, 1H), 4.74 (d, J= 8.6 Hz, 1H), 4.34 (t, J= 7.1 Hz, 1H), 4.20 (q, J= 9.5 Hz, 1H), 4.02 (d, J= 9.8 Hz, 1H), 3.83 (dt, J= 9.6, 4.4 Hz, 1H), 3.77-3.69 (m, 2H), 3.66 (d, J = 11.4 Hz, 6H), 3.62 - 3.52 (m, 5H), 3.50 (q, J= 4.1, 3.3 Hz, 4H), 3.39 (t, J= 6.0 Hz, 2H), 3.20 (dd, J= 9.1, 5.4 Hz, 3H), 2.99 (t, J = 8.5 Hz, 1H), 2.77 (t, J = 5.9 Hz, 2H), 2.20 - 2.10 (m, 1H), 1.88 - 1.64 (m, 7H), 1.46 (d, J = 13.3 Hz, 4H), 1.28 - 1.03 (m, 12H). 31PNMR (162 MHz, DMSO-t / ,) 5 145.03. Example 2: Synthesis of siRNA The siRNA of the present invention was prepared using the solid-phase phosphoramidite method well known in the art. The specific methods can be referred to, for example, PCT Publication Nos. WO2016081444 and WO2019105419, and are briefly described below. 1.1 Synthesis of Sense Strand (SS) Using the solid-phase phosphoramidite method, a blank CPG solid support was used as the starting cycle, and nucleoside monomers (including the monomer compound of the present invention and GalNAc delivery moiety) were linked one by one according to the arrangement of sense strand nucleotides from the 3' to 5' direction. Each linkage of a nucleoside monomer involved four steps of deprotection, coupling, capping, and oxidation or thiolation to synthesize 5 pmol oligonucleotide. The synthesis conditions were as follows: Nucleoside monomers were provided in a 0.05 mol / L acetonitrile solution. The conditions for each step were identical: 25°C; deprotection for 3 times using a 3% trichloroacetic acid-dichloromethane solution; coupling twice using a 0.25 mol / L 5-(ethylthio)-IH-tetrazole (ETT)-acetonitrile solution as an activator; capping twice using 10% acetic anhydride-acetonitrile and pyridine / N-methylimidazole / acetonitrile (10:14:76, v / v / v); oxidation twice using 0.05 mol / L of iodine in tetrahydrofuran / pyridine / water (70:20:10, v / v / v); thiolation twice using 0.2 mol / L phenylacetyl disulfide (PADS) in acetonitrile / 3-methylpyridine (1:1, v / v). 1.2 Synthesis of Antisense Strand (AS) Using the solid-phase phosphoramidite method, a blank CPG solid support was used as the starting cycle, and nucleoside monomers (including the monomer compound of the present invention and GalNAc delivery moiety) were linked one by one according to the arrangement of antisense strand nucleotides from the 3' to 5' direction. Each linkage of a nucleoside monomer involved four steps of deprotection, coupling, capping, and oxidation or thiolation. The conditions for the synthesis of a 5 pmol oligonucleotide for the antisense strand were identical to those for the sense strand. 1.3 Purification and Annealing of Oligonucleotides 1.3.1 Ammonolysis The synthesized solid support (sense or antisense strand) was transferred to a 5 mL centrifuge tube, followed by the addition of 3% diethylamine / ammonia (v / v). The mixture was allowed to react in a thermostatic water bath at 3 5 °C (or 5 5 °C) for 16 h (or 8 h), and then fdtered. The solid support was washed three times with ethanol / water, 1 mL each time. The filtrate was concentrated by centrifugation, and the crude product was purified. 1.3.2 Purification The methods for purification and desalting are well known to those skilled in the art. For example, a strong anionic packing column can be used; a sodium chloride-sodium hydroxide system can be used for elution and purification. The product can be collected in tubes and desalted using a gel packing purification column. The elution system can be pure water. 1.3.3 Annealing The sense strand (SS) was mixed with the antisense strand (AS) at a molar ratio (SS / AS = 1 / 1.05) according to the instructions. The mixture was heated in a water bath to 70-95°C for 3-5 min, and then allowed to cool naturally to room temperature. The system was freeze-dried to obtain the product. For the dual-targetting siRNA of the present invention, annealing needs to be performed two times using the corresponding two antisense strands as described above. Test Examples The sequences used in the following test examples are as follows. Duplex No. Sequence (5'->3') (the upper strand is the sense strand above and the lower one is the antisense strand) DR002242 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-GL6 (SEQ ID NO: 1) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) DR009154 UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 3) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR002220 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmAm-L96 (SEQ ID NO: 5) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) DR011130 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-GL6 (SEQ ID NO: 6) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) DR011131 IBs-GmsCm-UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 7) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 2) DR007894 GL34s-CmsAmGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-GL34 (SEQ ID NO: 8) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) DR011135 GL34s-UmsCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL34 (SEQ ID NO: 9) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 2) Duplex No. Sequence (5'->3') (from top to bottom: the sense strand, the antisense strand 1, and the antisense strand 2) DR009371 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-rGdAdT- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 10) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009419 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-dTdTdT- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 11) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009421 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-(G2P)dAdT-UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 12) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm DR009423 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-BLl-IBs-GmsCm- UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 6 & 7) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009424 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-BLl-BLl-BLl-UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 13 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009434 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-dTdTdTdT- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 14) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009435 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-dTdTdTdTdT- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 15) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009436 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-dTdTdT-GmsCms- UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 16) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009437 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-dTdTdT-IBs-GmsCm-UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 17) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009438 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-dAdAdA- GmsCmsUmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 18) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009439 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-dTdCdA- GmsCmsUmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 19) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009440 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-dCdA-GmsCms- UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 20) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009159 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-BL5- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 21 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009163 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-GfAfUf- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 22) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009752 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-dTdTdTdT-IBs- GmsCmUmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 23) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009753 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-dCdA-IBs-GmsCm-UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 24) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009754 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-dAdCdA-IBs- GmsCm-UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NO: 25) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009755 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-BLl-dTdTdT-IBs-GmsCm-UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 6 & 26) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009756 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-BLl-dCdA-GmsCms-UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 13 & 27) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009640 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-BL7- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 13 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR009641 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-BL7-BL7-BL7- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 13 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DRO10539 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-BL8-BL8-BL8- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 13 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DRO10540 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-BL8- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 13 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DRO 11035 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmsAmsAm-BL9- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 13 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011125 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-BL12-IBs-GmsCm- UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 6 & 7) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011128 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-BL7-IBs-GmsCm- UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 6 & 7) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011129 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-BL8-IBs-GmsCm- UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 6 & 7) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011132 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-BLl- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 21 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011133 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-BLl-SPl- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 21 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011134 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-SPl-BLl-UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 21 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011136 GL34s-CmsAmGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-GL34-BLl- GL34s-UmsCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL34 (SEQ ID NOs: 8 & 9) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011137 GL34s-AmsAmCmAmGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-GL34- BLl-GL34s-GmsCmUmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL34 (SEQ ID NOs: 28 & 29) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011138 GL34s-CmsAmGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-GL34-BL7- GL34s-UmsCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL34 (SEQ ID NOs: 8 & 9) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011125 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-BL12-IBs-GmsCm- UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 6 & 7) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011128 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-BL7-IBs-GmsCm- UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 6 & 7) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011129 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-IB-BL8-IBs-GmsCm- UmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 6 & 7) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011132 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-BLl- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 21 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011133 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-BLl-SPl- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 21 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011136 GL34s-CmsAmGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-GL34-BLl- GL34s-UmsCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL34 (SEQ ID NOs: 8 & 9) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011137 GL34s-AmsAmCmAmGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-GL34- BLl-GL34s-GmsCmUmCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL34 (SEQ ID NOs: 28 & 29) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011138 GL34s-CmsAmGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-GL34-BL7- GL34s-UmsCmAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL34 (SEQ ID NOs: 8 & 9) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DRO11743 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-SP2-BLl-UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 21 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DRO11745 DL0370-NHC6s-CmsAmGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-SPl-BLl-UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 30 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DRO 11746 DL0368-NHC6s-CmsAmGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-SPl-BLl-UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 31 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DRO 11747 DL0346-NHC6s-CmsAmGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-SPl-BLl-UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 32 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DRO 11748 DL0391-NHC6s-CmsAmGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-SPl-BLl-UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 33 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DRO11755 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-SPl-BLl-SPl-UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 21 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DR011756 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-SPl-BL10- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 21 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DRO 11757 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-SPl-BLll-UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 21 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) DRO 14029 CmsAmsGmUmGfUmUfCfUfUmGmCmUmCmUmAmUmAmsAms-SPl- UmsCmsAmAmCfAmUfAfUfUmUmGmAmUmCmAmGmUmsAms-GL6 (SEQ ID NOs: 21 & 3) UmsUfsAmUmAmGfAmGmCmAmAmGmAmAfCmAfCmUmGmsUmsUm (SEQ ID NO: 2) UmsAfsCmUmGmAfUmCmAmAmAmUmAmUfGmUfUmGmAmsGmsCm (SEQ ID NO: 4) The abbreviations used herein have the meaning as follows: rA, rU, rG, and rC represent a natural adenine ribonucleotide, a uracil ribonucleotide, a guanine ribonucleotide, and a cytosine ribonucleotide, respectively. d represents that the right nucleotide is a deoxyribonucleotide. For example, dA, dT, dG, and dC represent an 5 adenine deoxyribonucleotide, a thymine deoxyribonucleotide, a guanine deoxyribonucleotide, and a cytosine deoxyribonucleotide, respectively. m represents that the left nucleotide is a 2'-OCH3 modified nucleotide. For example, Am, Um, Gm, and Cm represent 2'-OCH3 modified A, U, G, and C, respectively. f represents that the left nucleotide is a 2'-F modified nucleotide. For example, Af, Uf, Gf, and Cf represent 2'10 F modified A, U, G, and C, respectively. "s" represents that the flanking two nucleotides and / or delivery moiety are linked by a phosphorothioate group. VP represents that the right nucleotide is a vinylphosphate modified nucleotide. IB is as previously defined. L96 represents a GalNAc delivery moiety of the following structure well known in the art, wherein 15 represents a position linked to dsRNA by a phosphate group or a phosphorothioate group. See, for example, PCT Publication Nos. WO2009073809 and WO2009082607. represents a position GL6 represents a GalNAc delivery moiety of the following structure, wherein linked to dsRNA by a phosphate group or a phosphorothioate group: GL34 represents a GalNAc delivery moiety of the following structure, wherein and represent the position of connection to dsRNA via a phosphate group or a phosphorothioate group, and when GL34 is located at an end of the nucleic acid strand, the corresponding and are hydrogen. The preparation of the corresponding synthetic intermediate 10 SP1 represents found, for example, in PCT Publication No. WO2024255761. and the structure of the CN corresponding synthetic intermediate is DMTrO SP2 represents and the structure of the corresponding synthetic intermediate is DL0370 represents DL0368 represents DL0346 represents DL0391 represents NHC6 represents Example 3: Activity Screening in Primary Mouse Hepatocytes (PMHs) 1. Cellular Free Uptake PMHs of C57BL / 6 mice were isolated, counted, and plated in a 96-well plate at 90 pL / well (1 * 104 cells / well). Free uptake: 2 pL of 20 pM compound stock solution was diluted with 98 pL of Opti-MEM and mixed well by pipetting up and down for gradient dilution according to the experimental needs; 10 pL of the diluted compound was transferred to a 96-well plate, mixed well, and incubated in 5% CO2 incubator at 37°C for 24 h. 2. RNA Extraction and Fluorescence Quantitative PCR Cellular RNA was extracted using a nucleic acid extractor (Hangzhou Allsheng Instruments Co., Ltd., Auto-pure96) according to the protocol of the High-throughput Cellular RNA Extraction Kit (Fushenbio, FSF0035-CS). Reverse transcription was performed using the PrimeScript™ II 1st Strand cDNA Synthesis Kit (Takara, 6210B). Fluorescence quantitative PCR reaction was performed using the TaqMan™ Fast Advanced Master Mix (ABI, 4444965) in a 20 pL system (ABI, QuantStudio3), The information on the primers used is as follows:____________ Primer Name Sequence Information (5'-3') Fluorophore mTTR-PF GGGAAGACCGCGGAGTCT (SEQ ID NO: 34) / mTTR-PR CAGTTCTACTCTGTACACTCCTTCTACAAA (SEQ ID NO: 35) / mTTR-P CTGCACGGGCTCACCACAGATGA (SEQ ID NO: 36) 5'6-FAM, 3'BHQl mANGPTL3-PF GAGCACCAAGAACTACTCCCC (SEQ ID NO: 37) / mANGPTL3-PR CACGCCACTTGTATGTTCGC (SEQ ID NO: 38) / mANGPTL3-P CCTTCCTGCCGACTGCTCTGCCGTTTA (SEQ ID NO: 39) 5'6-FAM, 3'BHQl mGAPDH-PF CGGCAAATTCAACGGCACAG (SEQ ID NO: 40) / mGAPDH-PR CCACGACATACTCAGCACCG (SEQ ID NO: 41) / mGAPDH-P ACCATCTTCCAGGAGCGAGACCCCACT (SEQ ID NO: 42) 5'TET, 3BHQ2 The residual inhibition was calculated using the following formula: The 2 AACt value was calculated and converted into a percentage to obtain the residual inhibition. AACt = [(Ct target gene of experimental group - Ct internal reference of experimental group) - (Ct target gene of control group - Ct internal reference of control group)]. The target genes were mTTR and mANGPTL3. The internal reference was mGAPDH. The control group was injected with saline. 3. Study Results The starting concentration of the siRNA component was 40 nM, and 11 concentration points were obtained by 4-fold gradient dilutions for screening the activity of the component in the cell line (free uptake for 24 h and 48 h). The experimental results are shown in the table below. Table 1. Activity Screening Results of siRNA Compound in PMHs - Free Uptake for 24 h and 48 h (mTTR) Compo und No. 40 nM 10 nM 2.5 nM 0.62 5 nM 0.15 625 nM 0.03 9 nM 0.009 76 nM 0.0024 nM 0.0006 1 nM 0.0001 52 nM 0.0000 381 nM mTTR IC50 (nM) DR002 242 1.0 % 1.8% 9.9% 36.2 % 67.4 % 86.7 % 97.9 % 95.9% 88.8% 95.7% 91.4% 0.3455 2 4 h DR009 154 97. 6% 98.3 % 105.0 % 103. 0% 104. 7% 105. 7% 106.2 % 106.6 % 100.6 % 102.0 % 87.5% NA DR009 159 6.9 % 26.0 % 64.4% 88.1 % 105. 0% 110. 7% 101.6 % 109.6 % 105.4 % 104.0 % 92.5% 4.1165 DR009 163 8.1 % 28.9 % 62.9% 85.4 % 99.8 % 104. 0% 103.0 % 101.5 % 95.2% 94.2% 90.0% 4.2605 DR002 220 0.9 % 1.6% 7.8% 32.8 % 64.0 % 87.6 % 96.9 % 100.9 % 98.5% 94.3% 89.6% 0.2950 DR009 338 1.2 % 2.5% 6.9% 18.9 % 54.9 % 92.5 % 114.7 % 138.4 % 124.3 % 114.4 % 108.0 % 0.1757 4 8 h DR009 339 0.9 % 1.8% 5.0% 19.2 % 52.9 % 99.7 % 124.2 % 111.4 % 125.6 % 117.7 % 96.5% 0.1789 DR009 371 0.7 % 1.6% 4.0% 13.7 % 41.7 % 78.2 % 120.8 % 121.6 % 131.8 % 112.1 % 109.5 % 0.1114 DR009 419 0.6 % 1.6% 2.0% 10.4 % 34.5 % 70.2 % 99.2 % 107.7 % 100.8 % 95.1% 104.2 % 0.0879 DR009 420 1.0 % 1.7% 4.2% 12.4 % 50.3 % 88.2 % 107.5 % 120.6 % 109.4 % 110.1 % 100.4 % 0.1508 DR002 242 0.6 % 1.0% 2.1% 4.3 % 12.2 % 35.5 % 79.0 % 110.6 % 134.5 % 105.5 % 101.3 % 0.0247 DR009 154 87. 1% 109.9 % 136.9 % 129. 4% 116. 4% 129. 7% 128.6 % 123.8 % 109.0 % 107.9 % 91.5% NA DR009 163 1.5 % 2.8% 9.0% 17.9 % 51.4 % 85.5 % 108.9 % 112.9 % 98.9% 101.1 % 108.1 % 0.1628 Table 2. Activity Screening Results of siRNA Compound in PMHs - Free Uptake for 24 h and 48 h (mANGPTL3) Compo und No. 40n M lOn M 2.5 nM 0.62 5 nM 0.15 625 nM 0.03 9 nM 0.00 976 nM 0.0024 nM 0.0006 1 nM 0.0001 52 nM 0.00003 81 nM mANG PTL3 IC50 (nM) DR002 242 97.8 % 108. 4% 106. 8% 113. 2% 103. 8% 109. 9% 117. 5% 107.6% 100.9 % 98.1% 96.1% NA 2 4 h DR009 154 31.8 % 52.9 % 87.1 % 113. 6% 125. 2% 144. 4% 129. 4% 122.6% 114.0 % 108.6 % 102.0% 12.208 DR009 159 53.4 % 83.0 % 112. 1% 123. 0% 125. 9% 131. 3% 127. 2% 127.6% 111.5 % 108.4 % 96.1% 44.948 DR009 163 54.3 % 85.0 % 103. 5% 117. 6% 112. 9% 120. 7% 119. 3% 113.0% 103.3 % 100.2 % 94.5% 46.835 DR002 220 98.5 % 104. 7% 110. 1% 111. 3% 109. 3% 108. 7% 114. 3% 108.7% 104.1 % 97.2% 97.8% NA DR009 338 9.5 % 19.6 % 35.1 % 65.3 % 89.6 % 104. 0% 108. 9% 104.6% 109.1 % 86.8% 84.9% 1.2474 4 8 h DR009 339 9.3 % 16.2 % 35.7 % 78.1 % 102. 2% 102. 6% 115. 3% 113.8% 109.0 % 89.4% 79.0% 1.5714 DR009 371 8.4 % 14.2 % 28.1 % 47.2 % 96.6 % 111. 5% 128. 8% 108.1% 114.7 % 95.5% 91.2% 0.6343 DR009 419 6.2 % 9.5 % 17.4 % 48.5 % 81.1 % 93.1 % 103. 2% 103.4% 86.7% 79.3% 90.0% 0.5989 DR009 420 9.9 % 16.9 % 36.7 % 67.3 % 112. 6% 119. 6% 124. 8% 112.0% 113.6 % 105.8 % 94.9% 1.2413 DR002 242 119. 7% 123. 7% 155. 9% 165. 4% 127. 5% 148. 6% 150. 8% 138.1% 135.5 % 114.3 % 96.9% NA DR009 154 7.5 % 13.1 % 23.9 % 41.8 % 72.5 % 102. 2% 136. 9% 132.6% 111.4 % 109.8 % 91.7% 0.4059 DR009 163 9.9 % 19.6 % 43.5 % 68.4 % 104. 1% 127. 1% 137. 3% 135.6% 121.9 % 116.2 % 107.5% 1.4590 Example 4: In Vivo Activity 1. Study Method C57BL / 6 mice (male, 18-21 g, 6-8 weeks) were randomly divided into 3 animals per saline control group and 5   3 animals per compound group, and were subcutaneously administered with the corresponding compound. At the corresponding days post-dose, about 10 mg of animal liver was removed and placed in RNAlater (5-10 times the tissue volume) at 4°C overnight, and then stored at -80°C for subsequent detection of mTTR and mANGPTL3 mRNA. The subsequent RNA extraction, qPCR detection, and calculation were the same as those in Example 3. 10 The experimental results were normalized to pre-dose levels. 2. Experimental Results (1st Experiment) Table 3. mTTR - Day 14 mANGPTL 3 - Day 14 Duplex No. Dose Residual Inhibition SD Residual Inhibition SD DR002242+ DR009154 1 mg / kg each 1.94% 0.50% 16.03% 5.80% DR009159 2 mg / kg 12.91% 4.70% 44.15% 4.90% DR009163 2 mg / kg 8.54% 5.43% 35.80% 9.44% Table 4. mTTR - Day 14 mANGPTL 3 - Day 14 Duplex No. Dose Residual Inhibition SD Residual Inhibition SD DR002242+ DR009154 1 mg / kg each 5.4% 0.9% 26.2% 1.6% DR009371 2 mg / kg 13.5% 2.3% 32.7% 3.8% DR009419 2 mg / kg 13.1% 2.5% 39.1% 4.0% DR009421 2 mg / kg 16.4% 3.1% 24.7% 4.1% DR009423 2 mg / kg 7.5% 0.8% 29.2% 4.0% DR009424 2 mg / kg 7.7% 0.5% 30.2% 0.9% DR009434 2 mg / kg 7.4% 1.3% 26.4% 3.7% DR009435 2 mg / kg 8.2% 4.1% 29.4% 11.2% DR009436 2 mg / kg 16.4% 11.6% 41.8% 8.6% DR009437 2 mg / kg 6.4% 1.5% 32.6% 7.6% DR009438 2 mg / kg 18.5% 8.7% 37.2% 6.8% DR009439 2 mg / kg 11.4% 2.7% 26.8% 3.2% DR009440 2 mg / kg 7.2% 3.0% 20.6% 5.7% 3. Experimental Results (2st Experiment) Table 5. mTTR - Day 14 mTTR - Day 28 mTTR - Day 42 Duplex No. Dose Residual Inhibition SD Residual Inhibition SD Residual Inhibition SD saline - 100.2% 7.0% 100.2% 7.2% 101.2% 17.1 % DR002242+ DR009154 1 mg / kg each 6.2% 1.7% 6.3% 1.3% 20.3% 8.3% DR009754 2 mg / kg 19.6% 11.6% 21.0% 1.8% 51.3% 5.8% DR009752 2 mg / kg 15.2% 3.6% 39.5% 8.1% 53.4% 6.2% DR009753 2 mg / kg 11.7% 2.4% 19.5% 3.9% 51.2% 7.9% DR009755 2 mg / kg 13.7% 4.5% 26.5% 8.9% 46.1% 8.4% DR009756 2 mg / kg 15.8% 2.7% 36.0% 7.5% 84.2% 5.1% DR009640 2 mg / kg 13.0% 2.6% / / / / DR009641 2 mg / kg 6.5% 1.4% / / / / Table 6. mANGPTL 3 - Day 14 mANGPTL3 - Day 28 mANGPTL3-Day 42 Duplex No. Dose Residual Inhibition SD Residual Inhibition SD Residual Inhibition SD saline - 100.7% 12.8% 100.3% 8.3% 100.8% 14.0% DR002242+ DR009154 1 mg / kg each 25.7% 2.9% 31.6% 5.7% 54.6% 7.3% DR009754 2 mg / kg 49.7% 17.8% 43.3% 7.6% 66.6% 8.0% DR009752 2 mg / kg 58.6% 7.3% 65.4% 9.6% 75.2% 10.2% DR009753 2 mg / kg 55.1% 6.7% 43.3% 3.0% 72.9% 10.2% DR009755 2 mg / kg 56.0% 15.0% 53.4% 8.5% 73.6% 8.1% DR009756 2 mg / kg 46.3% 4.6% 46.6% 4.0% 70.9% 5.8% DR009640 2 mg / kg 47.0% 3.2% / / / / DR009641 2 mg / kg 31.9% 4.8% / / / / 4. Experimental Results (3 rd Experiment) Table 7. mTTR - Day 7 mTTR - Day 14 mTTR - Day 28 mTTR - Day 42 Duplex No. Dose Residual Inhibition SD Residual Inhibition SD Residual Inhibition SD Residual Inhibition SD saline - 114.7% 9.2% 94.5% 16.2% 106.7% 5.7% 127.8% 15.4% DR002242+ DR009154 1 mg / kg each 4.8% 0.9% 2.4% 0.3% 3.7% 0.6% 11.5% 1.6% DR009641 2 mg / kg 7.4% 1.2% 7.9% 0.2% 18.8% 5.7% 70.0% 24.9% DR010539 2 mg / kg 5.8% 0.3% 7.9% 2.5% 17.6% 9.2% 62.6% 20.2% DR010540 2 mg / kg 5.6% 2.5% 7.8% 4.0% 19.9% 6.3% 64.3% 17.0% Table 8. mANGPTL3 - Day 7 mANGPTL 3 - Day 14 mANGPTL3 - Day 28 mANGPTL3 - Day 42 Duplex No. Dose Residual SD Residual SD Residual SD Residual SD Inhibition Inhibition Inhibition Inhibition saline - 98.2% 7.0 % 107.1% 16.1% 110.1% 13. 6% 155.1% 6.1% DR002242+ DR009154 1 mg / kg each 23.4% 2.6 % 13.3% 4.4% 17.9% 2.6 % 41.7% 6.8% DR009641 2 mg / kg 31.7% 5.2 % 24.5% 5.8% 30.8% 6.0 % 55.8% 18.9% DRO10539 2 mg / kg 19.7% 4.9 % 23.8% 13.1% 34.6% 11. 9% 63.3% 10.4% DRO10540 2 mg / kg 25.7% 10. 0% 23.3% 8.6% 31.3% 13. 6% 68.2% 23.0% Example 5: In Vivo Activity 1. Study Method C57BL / 6 mice (male, 18-21 g, 6-8 weeks) were randomly divided into 3 animals per saline control group and 5   3 animals per compound group, and were subcutaneously administered with the corresponding compound. At the corresponding days post-dose, blood was collected from the orbital venous plexus of mice, and serum mTTR and mANGPTL3 protein levels were detected according to the operation manual of the ELISA kit (Abeam Cat# ab282297, Sangon Cat# D721176). The experimental results were normalized to pre-dose levels. 10         2. Experimental Results (1st Experiment) Table 9. mTTR - Day 14 mTTR - Day 28 Duplex No. Dose Residual Inhibition SD Residual Inhibition SD saline - 91.80% 5.45% 97.43% 4.60% DR002242+DR009154 2 mg / kg each 1.46% 0.19% 2.30% 0.56% DRO1113O+DRO11131 4 mg / kg 1.10% 0.28% 2.62% 0.96% DR007894+DR011135 4 mg / kg 1.64% 0.33% 4.38% 0.51% DRO 11035 4 mg / kg 3.60% 0.69% 11.40% 3.74% DR009423 4 mg / kg 4.20% 0.89% 7.04% 0.90% DR009641 4 mg / kg 3.25% 0.66% 15.03% 1.49% DR011125 4 mg / kg 7.59% 3.65% 7.00% 0.19% DR011128 4 mg / kg 4.90% 1.73% 9.48% 1.02% DR011129 4 mg / kg 4.30% 0.30% 6.80% 1.31% DR011132 4 mg / kg 7.68% 3.96% 12.83% 7.74% DR011133 4 mg / kg 3.74% 0.53% 6.70% 0.39% DR011134 4 mg / kg 3.19% 0.93% 5.13% 0.85% DR011136 4 mg / kg 3.18% 0.77% 6.03% 0.69% DR011137 4 mg / kg 3.53% 1.99% 7.14% 3.32% DR011138 4 mg / kg 2.39% 0.43% 5.42% 0.31% Table 10. mANGPTL 3 - Day 14 mANGPTL3 Day 28 Duplex No. Dose Residual Inhibition SD Residual Inhibition SD saline - 66.35% 6.50% 87.07% 18.04% DR002242+ DR009154 2 mg / kg each 10.36% 5.58% 17.79% 7.19% DR011130+DR011131 4 mg / kg 5.60% 1.62% 14.92% 9.95% DR007894+DR011135 4 mg / kg 11.66% 6.58% 31.35% 2.88% DRO11035 4 mg / kg 18.31% 5.86% 47.22% 9.32% DR009423 4 mg / kg 24.03% 6.41% 36.72% 11.63% DR009641 4 mg / kg 10.67% 3.28% 32.33% 4.11% DR011125 4 mg / kg 28.05% 3.58% 50.65% 5.40% DR011128 4 mg / kg 25.29% 6.22% 54.25% 7.46% DR011129 4 mg / kg 25.94% 5.99% 42.46% 8.95% DR011132 4 mg / kg 36.29% 5.90% 53.06% 14.37% DR011133 4 mg / kg 13.72% 3.52% 36.42% 8.23% DR011134 4 mg / kg 8.31% 0.38% 42.34% 5.01% DR011136 4 mg / kg 18.80% 5.21% 50.85% 4.37% DR011137 4 mg / kg 23.65% 4.66% 38.59% 13.35% DR011138 4 mg / kg 14.19% 3.76% 49.28% 4.36% 3. Experimental Results (2nd Experiment) Table 11. mTTR - Day 14 mTTR - Day 28 mTTR - Day 42 Duplex No. Dose Residual Inhibition SD Residual Inhibition SD Residual Inhibition SD saline - 151.06% 15.32% 122.17% 22.98% 146.72% 32.54% DR002242+ DR009154 2 mg / kg each 0.89% 0.29% 1.60% 0.14% 5.37% 0.09% DR009641 4 mg / kg 2.36% 0.84% 11.21% 5.13% 37.21% 17.22% DR011134 4 mg / kg 2.82% 0.21% 4.52% 1.18% 10.68% 4.15% DRO 11743 4 mg / kg 2.07% 0.70% 3.44% 1.18% 10.29% 1.97% DRO 11745 4 mg / kg 2.56% 0.38% 5.77% 0.71% ND ND DRO 11746 4 mg / kg 2.73% 1.19% 9.26% 8.58% ND ND DRO 11747 4 mg / kg 2.67% 0.84% 4.96% 2.85% ND ND DRO 11748 4 mg / kg 4.25% 0.97% 10.43% 8.31% ND ND DRO 11752 4 mg / kg 5.95% 4.17% 13.96% 16.14% ND ND DRO 11754 4 mg / kg 9.48% 3.10% 16.36% 5.38% ND ND DRO 11755 4 mg / kg 2.19% 0.57% 5.41% 0.49% 7.44% 2.23% 5 Table 12. mANGPTL 3 - Day 14 mANGPTL3 - Day 28 mANGPTL3 - Day 42 Duplex No. Dose Residual Inhibition SD Residual Inhibition SD Residual Inhibition SD saline - 104.57% 27.15% 82.67% 28.84% 113.07% 32.44% DR002242+ DR009154 2 mg / kg each 3.81% 1.08% 6.74% 3.89% 20.67% 8.84% DR009641 4 mg / kg 14.86% 5.05% 25.18% 4.20% 53.42% 5.90% DR011134 4 mg / kg 18.59% 3.02% 22.49% 3.19% 51.71% 2.93% DRO 11743 4 mg / kg 17.91% 7.08% 36.39% 15.17% 45.99% 11.39% DRO 11745 4 mg / kg 24.02% 6.63% 37.72% 3.39% ND ND DRO 11746 4 mg / kg 22.33% 9.56% 38.74% 12.32% ND ND DRO 11747 4 mg / kg 19.73% 7.13% 36.90% 13.57% ND ND DRO11748 4 mg / kg 27.52% 14.33% 43.85% 6.49% ND ND DRO11752 4 mg / kg 33.56% 3.43% 48.16% 11.87% ND ND DRO 11754 4 mg / kg 49.90% 0.75% 62.24% 4.77% ND ND DRO 11755 4 mg / kg 21.18% 5.77% 29.88% 3.96% 34.88% 9.22% ND = not detected 4. Experimental Results (3 rd Experiment) Table 13. mTTR - Day 14 Duplex No. Dose Residual Inhibition SD saline - 126.01% 7.45% DR002242+ DR009154 2 mg / kg each 0.96% 0.24% DRO 14029 4 mg / kg 2.83% 1.21% DR011756 4 mg / kg 4.20% 2.03% 5 Table 14. mANGPTL3 - Day 14 Duplex No. Dose Residual Inhibition SD saline - 97.30% 25.63% DR002242+ DR009154 2 mg / kg each 6.01% 6.35% DRO 14029 4 mg / kg 17.87% 1.33% DR011756 4 mg / kg 22.33% 4.85% The above content is a further detailed description of the present invention in conjunction with specific preferred embodiments, but it cannot be regarded that the specific embodiments of the present invention are limited to these descriptions. For a person of ordinary skill in the art to which the present invention belongs, without 10 departing from the idea of the present invention, a number of simple deductions or replacements may be made, which should be regarded as falling within the protection scope of the present invention.

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof:Gi S, X S2 G2 qwherein Gi and G2 are each independently a nucleic acid molecule;Si and S2 are each independently a bond, -(OCH2CH2)k-, -(CH2CH2O)k-, -O(CH2CH2O)k-, or -(CH2)k-;k is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;X is a bond or a linker;preferably, Si and S2 are each independently a bond or -O(CH2CH2O)k-, wherein k is 1, 2, 3, 4, 5, 6, 7, or 8; preferably, Si and S2 are each independently a bond, -O(CH2CH2O)3-, or -O(CH2CH2O)6-.

2. A compound according to claim 1, wherein X comprises one or more compounds selected from formula (1-1) or formula (1-2), or a tautomer or stereoisomer thereof:wherein,ring A is selected from C5-10 cycloalkyl, 5-membered to 10-membered heterocyclyl, Ce-io aryl, or 5membered to 10-membered heteroaryl, preferably Ce-io aryl or 5-membered to 10-membered heteroaryl;Tg is selected from -S-Rt, -S-S-Rt, -OCH2-S-S-Rt, a sugar moiety, or a polypeptide;Rt is selected from H, C1-6 alkyl, or C1-6 haloalkyl;the sugar moiety is a sugar that can be cleaved in the inclusion or lysosome, preferably a five- or sixmembered sugar;the polypeptide is a group comprising 1, 2, 3, 4, or 5 amino acid residues;Lo is selected from -NRc-, C(O), -OC(O)NRc-, -C(O)NRc-, -NRcC(O)-, -NRc-C(O)O-, or -C(O)NRc-C(O)-;Li and L2 are linkers, preferably each independently selected from a bond, -(CH2)P-, -O-(CH2)P-, -(CH2)P-O-, -O-(CH2)P-O-(CH2)q-, -O-(CH2)p-NHCO-, -(CH2)q-(OCH2CH2)P-, -(CH2CH2O)P-, -O(CH2CH2O)P-, -NHC(O)-, -C(O)NH-, -OC(O)-, -C(O)O-, -S-S-, -NHC(O)O-, -NHC(O)NH-, -OC(O)O-, -OC(O)NH-, -O-CH(CH(OH)CH2OH)-, -O-CH(CH(NH2)CH2OH)-, -O-CH(CH2OH)CH(OH)-, -NH-CH(CH2OH)CH(OH)-, -O-CH2CH(OH)CH(OH)-, -O-CH2CH(NH2)CH(OH)-, -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-, -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-, -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-, or -NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-;Li and L2 are optionally substituted with 1, 2, or 3 substituents selected from halogen, OH, NH2, -C1-6 alkylene OH, -C1-6 alkylene NH2, C1-6 alkyl, or C1-6 haloalkyl;w is selected from 0, 1, 2, 3, or 4;p and q are each independently 1, 2, 3, 4, 5, or 6;wherein and in formula (I-1) or formula (1-2) are connected to Gi or G2 via abridged linkage;preferably represents connection to Gi via a bridged linkage (Si), and       in formula (1-1) or formula(1-2) represents connection to G2 via a bridged linkage (S2);Ra, Rb, and Re are independently selected from H, D, halogen, C1-6 alkyl, or C1-6 haloalkyl, and are optionally deuterated or fully deuterated.

3. A compound according to claim 1, wherein X comprises one or more compounds of formula (II), ora tautomer or stereoisomer thereof:wherein Tg is -S-S-C(Rd)3, -OCH2-S-S-C(Rd)3, a sugar moiety, or a polypeptide;the sugar moiety is preferably a sugar that can be cleaved in the inclusion or lysosome, preferably a five-or six-membered sugar, more preferably a six-membered sugar, more preferably selected from N-acetylgalactosamine, galactose, A-acctylglucosaminc. glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose;the polypeptide is selected from -(AA)a-R, -NH(AA)a-R, -(AA)a-C(O)R, -NH(AA)a-C(O)R, or -C(O)-NH(AA)a-C(O)NR;wherein each AA is independently selected from amino acid residues, preferably each AA is independently selected from natural amino acid residues;a is selected from 1, 2, 3, or 4;R is selected from H, D, halogen, Ci-6 alkyl, or Ci-6 haloalkyl, wherein R may be optionally deuterated or fully deuterated;Ra, Rb, and Re are independently selected from H, D, halogen, Ci-6 alkyl, or Ci-6 haloalkyl, and are optionally deuterated or fully deuterated;each Rd is independently selected from H, D, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, or a GalNAc-containing chain, and is optionally deuterated or fully deuterated;wherein Li and L2 are linkers, preferably each independently selected from a bond, -(CH2)P-, -O-(CH2)P-, -(CH2)p-O-, -O-(CH2)P-O-(CH2)q-, -O-(CH2)p-NHCO-, -(OCH2CH2)p-, -(CH2CH2O)p-, -O(CH2CH2O)p-, -NHC(O)-, -C(O)NH-, -OC(O)-, -0(0)0-, -S-S-, -NHC(0)0-, -NHC(0)NH-, -00(0)0-, -0C(0)NH-, -0-CH(CH(0H)CH20H)-, -O-CH(CH(NH2)CH2OH)-, -0-CH(CH20H)CH(0H)-, -NH-CH(CH20H)CH(0H)-, -0-CH2CH(0H)CH(0H)-, -O-CH2CH(NH2)CH(OH)-, -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-, -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-, -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-, -NHC(0)-CH2-NH-CH(CH20H)CH(0H)-, -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-, or -NHC(0)-CH2-0-CH2CH(NH2)CH(OH)-;wherein p and q are each independently 1, 2, 3, 4, 5, or 6;wherein and in formula (II) are connected to Gi or G2 via a bridged linkage; preferablyrepresents connection to Gi via a bridged linkage (Si), and in formula (II) represents connection to G2 via a bridged linkage (S2);preferably,Tg is selected from -S-S-C(Rd)3, -OCH2-S-S-C(Rd)3, a sugar moiety, or a polypeptide;the sugar moiety is selected from A-acetylgalactosamine, galactose, A-acetylghicosamine, glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose;the polypeptide is -NH(AA)a-C(0)R;each AA is independently selected from a valine residue, an alanine residue, a glycine residue, a leucine residue, or an isoleucine residue, more preferably from a valine residue or an alanine residue;a is selected from 1, 2, or 3, preferably 2 or 3;R is selected from H, D, C1-6 alkyl, or C1-6 haloalkyl, preferably C1-6 alkyl, such as CH3;Ra, Rb, and Rc are each independently selected from H, D, C1-6 alkyl, or C1-6 haloalkyl, preferably H or C1-6 alkyl, such as H or CH3;each Rd is independently selected from H, D, C1-6 alkyl, or C1-6 haloalkyl, preferably C1-6 alkyl, such as CH3;Li is selected from -(CH2)P-, -0-(CH2)P-, -(CH2)P-0-, -O-(CH2)P-O-(CH2)q-, -0-(CH2)P-NHC0-, -(OCH2CH2)p-, -(CH2CH2O)p-, or -O(CH2CH2O)P-, preferably -O-(CH2)P-O-(CH2)q-, or -0-(CH2)P-NHC0-;L2 is selected from -(CH2)P-, -0-(CH2)P-, -(CH2)P-0-, -O-(CH2)P-O-(CH2)q-, -0-(CH2)P-NHC0-, -70WO 2025 / 157273                                   PCT / CN2025 / 074781(OCH2CH2)p-, -(CH2CH2O)p-, or -O(CH2CH2O)P-, preferably -(CH2)P-O-;each p is independently selected from 2, 3, 4, 5, or 6, preferably 4, 5, or 6;each p is independently selected from 1, 2, 3, 4, or 5, preferably 1, 2, or 3;represents connection to Gi via a bridged linkage (Si), and in formula (II) represents connection to G2 via a bridged linkage (S2);more preferably,Tg is selected from A-acetylgalactosamine, galactose, A-acetylghicosamine, glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose;Ra, Rb, and Rc are each independently selected from H, D, Ci-6 alkyl, or Ci-6 haloalkyl, preferably H or Ci-6 alkyl, such as H or CH3;each Ra is independently selected from H, D, C1-6 alkyl, or C1-6 haloalkyl, preferably C1-6 alkyl, such as C(CH3)3;Li is selected from -(CH2)P-, -O-(CH2)P-, -(CH2)P-O-, -O-(CH2)p-O-(CH2)q-, -O-(CH2)P-NHCO-, -(OCH2CH2)p-, -(CH2CH2O)p-, or -O(CH2CH2O)P-, preferably -O-(CH2)p-O-(CH2)q-, or -O-(CH2)P-NHCO-;L2 is selected from -(CH2)P-, -O-(CH2)P-, -(CH2)P-O-, -O-(CH2)p-O-(CH2)q-, -O-(CH2)P-NHCO-, -(OCH2CH2)p-, -(CH2CH2O)p-, or -O(CH2CH2O)P-, preferably -(CH2)P-O-;each p is independently selected from 2, 3, 4, 5, or 6, preferably 4, 5, or 6;each p is independently selected from 1, 2, 3, 4, or 5, preferably 1, 2, or 3;represents connection to Gi via a bridged linkage (Si), and in formula (II) represents connection to G2 via a bridged linkage (S2).

4. A compound according to claim 3, provided that:1) Tg is -S-S-C(CH3)3;ii) Tg is galactose, glucose, A-acetylgalactosamine, or A-acetylglucosamine, preferably galactose OH                                 OHHO <                                 HO (( oh ) or A-acetylgalactosamine ( NHAc y Or3) Tg is -NH(AA)a-C(O)R, such as H 0 = H ;wherein each AA is independently selected from valine or alanine;a is selected from 1, 2, or 3, preferably 2 or 3;R is selected from H or C1-6 alkyl, such as CH3.

5. A compound according to any one of claims 2 to 4, wherein Ra, Rb, and Rc are each independently selected from H, D, halogen, or C1-6 alkyl, Li and L2 are each independently selected from a bond, -(CH2)P-, -O-(CH2)P-, -(CH2)P-O-, -O-(CH2)p-O-(CH2)q-, or -O-(CH2)P-NHCO-, and p and q are each independently 1, 2, 3, 4, 5, or 6.

6. A compound according to claim 1, wherein X comprises one or more compounds of formula (III), or a tautomer or stereoisomer thereof:wSg-L3x l5^ \ "O x (in)wherein Sg is a sugar moiety, preferably a sugar that can be cleaved in the inclusion or lysosome, preferably a five- or six-membered sugar, more preferably a six-membered sugar, more preferably selected from A-acetylgalactosamine, galactosamine, galactose, A'-acctylglucosaminc. glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose;L3 and L4 are linkers, preferably each independently selected from a bond, -(CH2)i-, -O-(CH2)i-, -(CH2)i-O-, -O-(CH2)i-O-(CH2)j-, -O-(CH2)i-NHCO-, -(OCH2CH2)i-, -(CH2CH2O)i-, -O(CH2CH2O)i-, -(CH2)j-71(OCH2CH2)i-, -NHC(O)-, -C(O)NH-, -C(O)-, -OC(O)-, -C(O)O-, -S-S-, -NHC(O)O-, -NHC(O)NH-, -OC(O)O-, -OC(O)NH-, -O-CH(CH(OH)CH2OH)-, -O-CH(CH(NH2)CH2OH)-, -O-CH(CH2OH)CH(OH)-, -NH-CH(CH2OH)CH(OH)-, -O-CH2CH(OH)CH(OH)-, -O-CH2CH(NH2)CH(OH)-, -NHC(O)-CH2-O-CH(CH(OH)CH2OH)-, -NHC(O)-CH2-O-CH(CH(NH2)CH2OH)-, -NHC(O)-CH2-O-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-NH-CH(CH2OH)CH(OH)-, -NHC(O)-CH2-O-CH2CH(OH)CH(OH)-, or -NHC(O)-CH2-O-CH2CH(NH2)CH(OH)-;wherein i and j are each independently 1, 2, 3, 4, 5, or 6;L5 is a linker, preferably selected from a bond, C3-7 cycloalkyl, Ce-io aryl, 3-membered to 7-membered heterocyclyl, or 5-membered to 10-membered heteroaryl, more preferably, L5 is selected from a bond, C5-6 cycloalkyl, Ce-io aryl, 5-membered to 6-membered heterocyclyl containing 1 to 3 heteroatoms, or 5-membered to 6-membered heteroaryl containing 1 to 3 heteroatoms, wherein the heteroatom is N or O;wherein and in formula (III) are connected to Gi or G2 via abridged linkage; preferablyrepresents connection to Gi via a bridged linkage (Si), and in formula (III) represents connection to G2 via a bridged linkage (S2);preferably,Sg is selected from N-acetylgalactosamine, galactose, galactosamine, N-acetylglucosamine, glucose, mannose, glucuronic acid, neuraminic acid (sialic acid), xylose, or fucose, e.g. N-acetylgalactosamine or OH H°( 0H0 hC / 0  '—\L3 is selected from a bond, -(CH2)i-, -O-(CH2)i-, -(CH2)i-O-, -O-(CH2)i-O-(CH2)j-, -O-(CH2)i-NHCO-, -(OCH2CH2)i-, -(CH2CH2O)i-, -O(CH2CH2O)i-, or -(CH2)j-(OCH2CH2)i-;L4 is selected from a bond , -(CH2)i-, -O-(CH2)i-, -(CH2)i-O-, -O-(CH2)i-O-(CH2)j-, -O-(CH2)i-NHCO-, -(OCH2CH2)i-, -(CH2CH2O)i-, -O(CH2CH2O)i-, -NHC(O)-, -C(0)NH-, -C(O)-, -OC(O)-, -C(O)O-, -S-S-, -NHC(0)0-, -NHC(0)NH-, -OC(O)O-, or -0C(0)NH-;each i is independently selected from 1, 2, 3, 4, 5, or 6;each j is independently selected from 1, 2, 3, 4, 5, or 6;L5 is selected from a bond, C5-6 cycloalkyl, Ce-io aryl, 5-membered to 6-membered heterocyclyl containing 1 to 3 heteroatoms, or 5-membered to 6-membered heteroaryl containing 1 to 3 heteroatoms, wherein the heteroatom is N or O;represents connection to Gi via a bridged linkage (Si), and in formula (III) represents connection to G2 via a bridged linkage (S2).

7. A compound according to claim 6, wherein X comprises one or more compounds of formula (Illa),or a tautomer or stereoisomer thereof:L3 is selected from a bond, -(CH2)i-, -(CH2)i-O-, -O-(CH2)i-O-(CH2)j-, -(OCH2CH2)i-, -(CH2CH2O)i-, -O(CH2CH2O)i-, or -(CH2)j-(OCH2CH2)i-;L4 is selected from a bond, -NHC(O)-, -C(0)NH-, -C(O)-, -OC(O)-, -C(O)O-, -S-S-, -NHC(0)0-, -NHC(0)NH-, -OC(O)O-, or -0C(0)NH-;L5 is selected from a bond, C5-6 cycloalkyl, or 5-membered to 6-membered heterocyclyl containing 1 to 3 heteroatoms, wherein the heteroatom is N or 0;wherein i and j are each independently 1, 2, 3. 4, 5, or 6;72represents connection to Gi via a bridged linkage (Si), andin formula (Illa) representsconnection to G2 via a bridged linkage (S2).

8. A compound according to claim 6 or 7, provided that:i)ii)L3 is -(CH2)4-, L4 is a bond, and L5 is a bond;L3 is -(CH2)5-, L4 is -OC(O)-, and L5 is(such asL3 is -(CH2)4-, L4 is -C(O)-, and L5 isL3 is -CH2CH2-(OCH2CH2)2-, L4 is -NHC(O)-, and L5 isv)L3 is -CH2CH2-(OCH2CH2)2-, L4 is -OC(O)-, and L5 is10    9.A compound according to claim 1, wherein X comprises one or more of the following compounds:Compound No. Structure BL1 1                  a 1 OH               y 1 OH BL2 O A w        / « < V 0 —z BL3 H OH "°X oAJ OH BL4 J * o=( \ ( zr    \ ""% ) IZ     < y 0 >° —z BL5 y w / BL6 0 w-w BL7 0 HO   NHAc        n BL8 0                  __ H0   NHAc           0G2 via a bridged linkage (S2).

10. A compound according to claim 1, wherein X is a nucleotide linker, the nucleotide is selected from one or more of a deoxyribonucleotide, a ribonucleotide, a 2'-deoxy-2'-fluororibonucleotide, a 2'-5' ribonucleotide, and a 2'-5' deoxyribonucleotide.

11. A compound according to claim 10, wherein X is Nt(dN)m, wherein Nt is selected from a bond, a deoxyribonucleotide, a ribonucleotide, a 2'-deoxy-2'-fluororibonucleotide, or a 2'-5' ribonucleotide, each dN is independently selected from dA, dT, dG, or dC, and m is 1, 2, 3, 4, 5, 6, 7, or 8, preferably m is 1, 2, 3, 4, or 5.

12. A compound according to claim 11, wherein X is selected from (G2p)dAdT, rGdAdT, dCdA, dAdT, dAdCdA, dTdCdA, dAdAdA, dTdTdT, -GfAfUf-, dTdTdTdT, or dTdTdTdTdT, preferably selected from (G2p)dAdT, rGdAdT, dCdA, dAdT, dAdCdA, dTdCdA, dAdAdA, dTdTdT, dTdTdTdT, or dTdTdTdTdT.

13. A compound according to claim 1, wherein X is -(BL)p(dN)m-;wherein each BL is independently selected from a compound of formula (1-1) or (1-2) as defined in claim 2, a compound of formula (II) as defined in any one of claims 3 to 5, a compound of formula (III) as defined in any one of claims 6 to 8 or a tautomer or stereoisomer thereof, or BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, BL9, BL10, BL11, or BL12 as defined in claim 9 or a tautomer or stereoisomer thereof;each dN is independently selected from dA, dT, dG, or dC;p is selected from 0, 1, 2, 3, 4, 5, or 6, preferably 0, 1, 2, or 3;m is selected from 0, 1, 2, 3, 4, 5, 6, 7, or 8, preferably 0, 1, 2, 3, 4, or 5;p and m are not both 0;preferably, X is -(BL)p-;each BL is independently selected from a compound of formula (1-1) or (1-2) as defined in claim 2, a compound of formula (II) as defined in any one of claims 3 to 5, a compound of formula (III) as defined in any one of claims 6 to 8 or a tautomer or stereoisomer thereof, or BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, BL9, BL 10, BL11, or BL 12 as defined in claim 9 or a tautomer or stereoisomer thereof;p is selected from 0, 1, 2, 3, 4, 5, or 6, preferably 0, 1, 2, or 3.

14. A compound according to claim 13, provided that:i) X is BL(dN)m, wherein BL is selected from BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, BL9, BL10, BL11, or BL 12, preferably BL1, dN is each independently selected from dA, dT, dG, or dC, and m is 1, 2, 3, 4, or 5;WO 2025 / 157273                                   PCT / CN2025 / 074781ii) X is selected from BLl-dTdTdT or BLl-dCdA;iii) X is (BL)P, wherein each BL is independently selected from BL1, BL2, BL3, BL4, BL5, BL6, BL7, BL8, or BL9, preferably BL7 or BL8, and p is 1, 2, or 3; oriv) X is BL1, -BL 1-BL 1-BL 1-, BL5, BL7, BL8, BL9, BL10, BL11, BL12, BL7-BL7-BL7, BL8-BL8-BL8, or BL9-BL9-BL9, preferably X is BL7, BL7-BL7-BL7, BL8, BL8-BL8-BL8, BL9, or BL9-BL9-BL9.

15. A compound according to any one of claims 1 to 14, wherein Gi and G2 are independently selected from a double-stranded nucleic acid molecule, preferably a dsRNA.

16. Acompound according to claim 15, wherein the dsRNAmolecule has a sense strand and an antisense strand, each having 14 to 30 nucleotides, wherein the antisense strand comprises a sequence sufficiently complementary to the sense strand and the target mRNA.

17. A compound according to claim 15 or 16, wherein Gi and G2 may target identical or different target mRNAs, preferably different target mRNAs.

18. A compound according to any one of claims 15 to 17, wherein Gi and G2 each have a sense strand connected to -S1-X-S2-.

19. A compound according to any one of claims 15 to 18, wherein the end of the sense strand of each of Gi and G2 optionally contains one or more terminal modifications, preferably the 5' end and / or 3' end of the sense strand of each of Gi and G2 optionally contains one or more terminal modifications.

20. A compound according to any one of claims 15 to 19, wherein the 5' end of the sense strand of Gi and the 5' end of the sense strand of G2 each contain a terminal modification.

21. A compound according to claim 19 or 20, wherein the terminal modification is selected from an abasic nucleotide (such as IB), an inverted nucleotide, and an optionally substituted         h ,preferably the optionally substituted h is substituted with a GalNAc-containing side chain substituent.

22. A compound according to any one of claims 19 to 21, wherein the terminal modification is selected from IB, STM1, GL6, or GL34.

23. A compound according to any one of claims 15 to 22, wherein the 3' end of the antisense strand of each of Gi and G2 is a blunt end or overhang, preferably an overhang, more preferably an overhang of both nucleotides.

24. A compound according to any one of claims 1 to 23, wherein X, Si, and S2 are as defined in Table A of the specification, preferably X, Si, S2, 5' terminal modification of Gi, 3' terminal modification of Gi, 5' terminal modification of G2, and 3' terminal modification of G2 are as defined in Table A of the specification.

25. A cell comprising a compound of any one of claims 1 to 24 or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof.

26. A pharmaceutical composition comprising a compound of any one of claims 1 to 24 or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, or a cell of claim 25, and optionally a pharmaceutically acceptable carrier or excipient.

27. A kit comprising a compound of any one of claims 1 to 24 or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, or a cell of claim 25.

28. The use of a compound according to any one of claims 1 to 24 or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof for the manufacture of a medicament for treating and / or preventing diseases.