WO2024033896A1

WO2024033896A1 - Oligonucleotides targeting indoleamine 2,3-dioxygenase and uses thereof

Info

Publication number: WO2024033896A1
Application number: PCT/IB2023/058154
Authority: WO
Inventors: Jin-Hyeob RYU; Mincheol Kwon
Original assignee: Biorchestra Co., Ltd.
Priority date: 2022-08-12
Filing date: 2023-08-11
Publication date: 2024-02-15

Abstract

The present disclosure relates to small interfering RNAs, which target IDO1 mRNA in a cell, leading to reduced expression of IDO1 protein. Reduction of IDO1 protein expression is beneficial for the treatment of certain medical disorders, e.g., a cancer or a neuronal disease.

Description

OLIGONUCLEOTIDES TARGETING INDOLEAMINE 2,3-DIOXYGENASE AND USES THEREOF REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application Number 63/371,343, filed on August 12, 2022. The entire disclosure of the above-referenced application is incorporated by reference in its entirety. REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY [0002] The content of the electronically submitted sequence listing (Name: 4366_066PC_SequenceListing_ST26.xml; Size: 37,540 bytes; and Date of Creation: August 1, 2023) is herein incorporated by reference in its entirety. FIELD OF THE DISCLOSURE [0003] The present disclosure relates to oligonucleotides, e.g., small interfering RNA molecules (siRNAs), that target indoleamine 2,3-dioxygenase (IDO1) mRNA transcript in a cell, leading to reduced expression of indoleamine 2,3-dioxygenase (IDO1) protein. Some aspects of the present disclosure are related to the use of such siRNAs to treat a wide range of diseases and disorders. BACKGROUND OF THE DISCLOSURE [0004] The tryptophan catabolism pathway plays an important role in tumor cell evasion of the innate and adaptive immune systems. Tryptophan is generally utilized in three major metabolic pathways: incorporation into proteins, production of serotonin, and breakdown into kynurenine. Indoleamine 2,3-dioxygenase (IDO1), is a tryptophan degrading enzyme that catalyzes the oxidative conversion of tryptophan to N-formyl kynurenine. IDO1 is expressed in many cell types including fibroblasts, mesenchymal stromal cells, and immune cells, such as monocytes, macrophages and dendritic cells. In these cells, expression of IDO1 is induced by inflammatory cytokines, in particular IFN-γ. Therefore, IDO1 plays an essential role in regulating tryptophan and kynurenine levels in response to inflammation from viral infection or the tumor microenvironment. IDO1 is overexpressed in tumor cells of the vast majority of cancers. Activity of IDO1 in the tumor microenvironment leads to the depletion of tryptophan and the production of kynurenine. Together, depletion of tryptophan and production of kynurenine reduce the antitumor response and promote neovascularization in the tumor microenvironment. T cells, a major component of the antitumor response, sense depletion of tryptophan by the kinase general control nonderepressible 2 (GCN2) which inhibits T cell proliferation upon activation. Tryptophan depletion also inhibits the mammalian target of rapamycin (mTOR), which triggers autophagy, leading to anergy in T cells in the tumor microenvironment. mTOR inhibition in CD4⁺ T cells also induces T regulatory cell (T_reg) differentiation. Additionally, kynurenine is an endogenous ligand of the aryl hydrocarbon receptor (AhR) which promotes naïve CD4⁺ T cell differentiation into Treg cells. Therefore, IDO1 depletion of tryptophan via the production of kynurenine contributes to an immunosuppressive tumor microenvironment. [0005] Due to the important role of IDO1 in the regulation of tryptophan level in the tumor microenvironment and tumor immune evasion, there has been great interest in targeting IDO1 as an anti-tumor treatment. Unfortunately, IDO1 inhibitor monotherapies have demonstrated limited efficacy in recent clinical trials. Thus, novel strategies for targeting IDO1 expression are needed. BRIEF SUMMARY OF THE DISCLOSURE [0006] The present disclosure is directed to a small interfering RNA (siRNA) comprising a contiguous nucleotide sequence of 14 to 22 nucleotides in length that is complementary to a nucleic acid sequence within an indoleamine 2,3-dioxygenase 1 (IDO1) transcript, wherein the IDO1 transcript is selected from SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, or a combination thereof. [0007] In some aspects, the small interfering RNA of the present disclosure is capable of binding to the IDO1 transcripts set forth in SEQ ID NOs: 1 and 3. In some aspects, the small interfering RNA of the present disclosure is capable of binding to the IDO1 transcripts set forth in SEQ ID NOs: 1, 3, and 5. In some aspects, the small interfering RNA of the present disclosure is capable of binding to the IDO1 transcripts set forth in SEQ ID NOs: 1, 3, 5, and 13. In some aspects, the small interfering RNA of the present disclosure is capable of binding to the IDO1 transcripts set forth in SEQ ID NOs: 1, 3, 5, 7, 9, and 13. [0008] In some aspects, the small interfering RNA of the present disclosure does not bind to: (i) the IDO1 transcript set forth in SEQ ID NO: 11, (ii) the IDO1 transcript set forth in SEQ ID NO: 13, or (iii) both (i) and (ii). In some aspects, the small interfering RNA of the present disclosure does not bind to: (i) the IDO1 transcript set forth in SEQ ID NO: 7, (ii) the IDO1 transcript set forth in SEQ ID NO: 9, or (iii) both (i) and (ii). In some aspects, the small interfering RNA of the present disclosure is capable of binding only to: (i) the IDO1 transcript set forth in SEQ ID NO: 1, (ii) the IDO1 transcript set forth in SEQ ID NO: 3, (iii) the IDO1 transcript set forth in SEQ ID NO: 5, or (iv) any combination of (i) to (iii). [0009] In some aspects, the small interfering RNA of the present disclosure is capable of binding to one or more nucleic acid sequences which comprises: (a) nucleotides 317-355 of SEQ ID NO: 1, (b) nucleotides 518-556 of SEQ ID NO: 1, (c) nucleotides 801-839 of SEQ ID NO: 1, (d) nucleotides 415-452 of SEQ ID NO: 1, (e) nucleotides 511-549 of SEQ ID NO: 3, (f) nucleotides 794-832 of SEQ ID NO: 3, (g) nucleotides 408-445 of SEQ ID NO: 3, (h) nucleotides 664-702 of SEQ ID NO: 5, (i) nucleotides 947-985 of SEQ ID NO: 5, (j) nucleotides 561-598 of SEQ ID NO: 5, (k) nucleotides 453-490 of SEQ ID NO: 7, (l) nucleotides 560-597 of SEQ ID NO: 9, (m) nucleotides 302-340 of SEQ ID NO: 13, (n) nucleotides 400-437 of SEQ ID NO: 13, or (o) a combination thereof. [0010] In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 811-829 of SEQ ID NO: 1. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 327-345 of SEQ ID NO: 1. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 425-442 of SEQ ID NO: 1. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 528-546 of SEQ ID NO: 1. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 804- 822 of SEQ ID NO: 3. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 418-435 of SEQ ID NO: 3. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 521-539 of SEQ ID NO: 3. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 957-975 of SEQ ID NO: 5. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 571-588 of SEQ ID NO: 5. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 674-692 of SEQ ID NO: 5. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 463- 480 of SEQ ID NO: 7. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 570-587 of SEQ ID NO: 9. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 312-330 of SEQ ID NO: 13. In some aspects, the small interfering RNA of the present disclosure comprises the nucleic acid sequence which comprises nucleotides 410-427 of SEQ ID NO: 13. In some aspects, the small interfering RNA of the present disclosure comprises the contiguous nucleotide sequence which comprises SEQ ID NO: 15 to SEQ ID NO: 18 with one, two, or three mismatches. [0011] In some aspects, the small interfering RNA of the present disclosure comprises the contiguous nucleotide sequence comprises SEQ ID NO: 15 to SEQ ID NO: 18. In some aspects, the contiguous nucleotide sequence comprises SEQ ID NO: 15. In some aspects, the contiguous nucleotide sequence comprises SEQ ID NO: 16. In some aspects, the contiguous nucleotide sequence comprises SEQ ID NO: 17. In some aspects, the contiguous nucleotide sequence comprises SEQ ID NO: 18. [0012] In some aspects, the small interfering RNA of the present disclosure is capable of binding to an IDO1 transcript, wherein the binding of the small interfering RNA to the IDO1 transcript is capable of inhibiting the expression of the IDO1 protein in a cell which comprises the IDO1 transcript. [0013] In some aspects, the small interfering RNA of the present disclosure is capable of reducing the conversion of tryptophan to kynurenine in a cell when contacted with the cell. In some aspects, the small interfering RNA is capable of increasing or stabilizing tryptophan levels in a cell when contacted with the cell. In some aspects, the small interfering RNA is capable of reducing or stabilizing kynurenine levels in a cell when contacted with the cell. [0014] In some aspects, the small interfering RNA of the present disclosure is capable of inhibiting the expression of the IDO1 protein in a cell which comprises the IDO1 transcript, wherein the cell comprises a neuronal cell, tumor cell, immune cell, endothelial cell, mesenchymal cell, fibroblast cell, any other cell of the tumor micro-environment, or any combination thereof. [0015] In some aspects, the small interfering RNA of the present disclosure comprises a contiguous nucleotide sequence, wherein the contiguous nucleotide sequence comprises at least one nucleotide analogue. [0016] In some aspects, the small interfering RNA of the present disclosure comprises at least one nucleotide analogue, wherein the nucleotide analogue or analogues are one or more sugar modified nucleosides comprises Locked Nucleic Acid (LNA); 2'-O-alkyl-RNA; 2'-amino-DNA; 2'-fluoro-DNA; arabino nucleic acid (ANA); 2'-fluoro-ANA, hexitol nucleic acid (HNA), intercalating nucleic acid (INA), constrained ethyl nucleoside (cEt), 2'-O-methyl nucleic acid (2'-OMe), 2'-O-methoxyethyl nucleic acid (2'-MOE), and any combination thereof. In some aspects, the small interfering RNA which comprise the nucleotide analogue or analogues comprise a bicyclic sugar. In some aspects, the small interfering RNA comprise a bicyclic sugar, wherein the bicyclic sugar comprises cEt, 2',4'- constrained 2′-O-methoxyethyl (cMOE), LNA, α-L-LNA, β-D-LNA, 2'-O,4'-C-ethylene- bridged nucleic acids (ENA), amino-LNA, oxy-LNA, or thio-LNA. In some aspects, the small interfering RNA comprise the nucleotide analogue or analogues, wherein the nucleotide analogue or analogues comprise an LNA. In some aspects, the small interfering RNA comprises one or more 5' methyl cytosine nucleobases. In some aspects, the small interfering RNA of the present disclosure comprises two to five LNAs on the 5' region of the small interfering RNA. In some aspects, the small interfering RNA comprises two to five LNAs on the 3' region of the small interfering RNA. [0017] In some aspects, the small interfering RNA of the present disclosure has 14, 15, 16, 17, 18, 19, 20, 21, or 22 nucleotides in length. In some aspects, the small interfering RNA has 14 nucleotides in length. In some aspects, the small interfering RNA has 19 nucleotides in length. In some aspects, the small interfering RNA has 20 nucleotides in length. [0018] In some aspects, the small interfering RNA of the present disclosure comprises an internucleoside linkage selected from: a phosphodiester linkage, a phosphotriester linkage, a methylphosphonate linkage, a phosphoramidate linkage, a phosphorothioate linkage, and combinations thereof. In some aspects, the small interfering RNA which comprises the internucleoside linkage comprises one or more stereo-defined, modified phosphate linkages. [0019] In some aspects, the small interfering RNA of the present disclosure comprises, consists essentially of, or consists of the contiguous nucleotide sequence set forth in any one of SEQ ID NOs: 15 to 18. In some aspects, the small interfering RNA comprises, consists essentially of, or consists of the contiguous nucleotide sequence set forth in SEQ ID NO: 15. In some aspects, the small interfering RNA comprises, consists essentially of, or consists of the contiguous nucleotide sequence set forth in SEQ ID NO: 16. In some aspects, the small interfering RNA comprises, consists essentially of, or consists of the contiguous nucleotide sequence set forth in SEQ ID NO: 17. In some aspects, the small interfering RNA of the present disclosure comprises, consists essentially of, or consists of the contiguous nucleotide sequence set forth in SEQ ID NO: 18. [0020] The present disclosure provides a conjugate comprising the small interfering RNA, wherein the small interfering RNA is covalently attached to at least one non-nucleotide or non-polynucleotide moiety. In some aspects, the conjugate comprises at least one non- nucleotide or non-polynucleotide moiety, wherein the non-nucleotide or non- polynucleotide moiety comprises a protein, a fatty acid chain, a sugar residue, a glycoprotein, a polymer, a steroid, or any combination thereof. [0021] The present disclosure provides a pharmaceutical composition comprising the small interfering RNA or the conjugate and a pharmaceutically acceptable carrier. [0022] The present disclosure also provides a kit comprising the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure, and instructions for use. [0023] The present disclosure provides a method of inhibiting or reducing IDO1 protein expression in a cell comprising the IDO1 transcript, the method comprising contacting the cell with the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure, wherein the IDO1 protein expression in the cell is inhibited or reduced after the contacting. In some aspects, the IDO1 protein expression is inhibited or reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference cell (e.g., corresponding cell that is not contacted and/or the cell prior to the contacting). In some aspects, the cell comprises a tumor cell, immune cell, endothelial cell, mesenchymal cell, fibroblast cell, any other cell of the tumor micro-environment, or any combination thereof. In some aspects, the contacting occurs ex vivo. In some aspects, the contacting occurs in vivo, which comprises administering the small interfering RNA, the conjugate, or the pharmaceutical composition to a subject in need thereof prior to the contacting. [0024] The present disclosure also provides a method of inhibiting or reducing IDO1 transcript level in a cell comprising the IDO1 transcript, the method comprising contacting the cell with the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure, wherein the IDO1 transcript level in the cell is inhibited or reduced after the contacting. In some aspects, the IDO1 transcript level is inhibited or reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference cell (e.g., corresponding cell that is not contacted and/or the cell prior to the contacting). In some aspects, the cell comprises a tumor cell, immune cell, endothelial cell, mesenchymal cell, fibroblast cell, any other cell of the tumor micro-environment, or any combination thereof. In some aspects, the contacting occurs ex vivo. In some aspects, the contacting occurs in vivo, which comprises administering the small interfering RNA, the conjugate, or the pharmaceutical composition to a subject in need thereof prior to the contacting. [0025] The present disclosure also provides a method of reducing the conversion of tryptophan to kynurenine in a cell of a subject in need thereof, comprising administering to the subject the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure. In some aspects, the conversion of tryptophan to kynurenine in the cell is reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). [0026] The present disclosure also provides a method of increasing or stabilizing tryptophan level in a cell or in the blood of a subject in need thereof, comprising administering to the subject the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure. In some aspects, the tryptophan level is increased by at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, at least about 10-fold, at least about 15-fold, at least about 20-fold, at least about 25-fold, at least about 30-fold, at least about 35-fold, at least about 40-fold, or at least about 50-fold, as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). [0027] The present disclosure also provides a method of reducing or stabilizing kynurenine level in a cell or in the blood of a subject in need thereof, comprising administering to the subject the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure. In some aspects, the kynurenine level is reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). [0028] The present disclosure also provides a method of treating a cancer in a subject in need thereof, comprising administering to the subject the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure. In some aspects, the method further comprises administering an additional therapeutic agent to the subject. In some aspects, the additional therapeutic agent comprises an anticancer agent (chemotherapy), radiation therapy, or a combination thereof. In some aspects, the anticancer agent comprises an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor comprises a CTLA-4 antagonist, a LAG-3 antagonist, a TIM3 antagonist, a TIGIT antagonist, a TIM3 antagonist, a NKG2a antagonist, an OX40 antagonist, an ICOS antagonist, a MICA antagonist, a CD137 antagonist, a KIR antagonist, a TGFβ antagonist, an IL-10 antagonist, an IL-8 antagonist, a B7-H4 antagonist, a Fas ligand antagonist, a CXCR4 antagonist, a mesothelin antagonist, a CD27 antagonist, a GITR antagonist, a PD-1 antagonist, a PD-L1 antagonist or any combination thereof. In some aspects, the anticancer agent comprises an angiogenesis inhibitor, wherein the angiogenesis inhibitor comprises a VEGF antagonist, a VEGFR antagonist, a FGF antagonist, a PDGF antagonist, a TGF antagonist, an angiopoietin antagonist, a HER2 antagonist, bevacizumab, axitinib, everolimus, cabozantinib, lenalidomide, lenvatinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, thalidomide, ziv-afibercept and vandetanib or any combination thereof. In some aspects, the anticancer agent comprises an adoptive cell therapy, wherein the adoptive cell therapy comprises T cells expressing a chimeric antigen receptor (CAR-T cells), NK cells expressing a chimeric antigen receptor (CAR-NK cells), any other immune cells expressing a chimeric antigen receptor, or any combination thereof. In some aspects, the anticancer agent (chemotherapy) comprises a topoisomerase inhibitor, a DNA methyltransferase inhibitor, a DNA intercalator, ixabepilone, bendamustine hydrochloride, eribulin mesylate, cabazitaxel, emtansine, trabectedin, nanoliposomal irinotecan, TAS-102, etoposide, carboplatin, cisplatin, doxorubicin, temozolomide or any combination thereof. [0029] The present disclosure also provides a method of treating a neuronal disease in a subject in need thereof, comprising administering to the subject the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure. In some aspects, the method further comprises administering an additional therapeutic agent to the subject. In some aspects, the additional therapeutic agent comprises an agent to treat a neuronal disease, wherein the agent comprises an acetylcholinesterase inhibitor, an NMDA antagonist, a dopamine supplement, a DOPA decarboxylase inhibitor, a Catechol-o- methyltransferase (COMT) inhibitor, a monoamine oxidase (MAO) inhibitor, an NMDA antagonist, an antioxidant, an antichorea drug, donepezil, rivastigmine, memantine, levodopa, carbidopa, benserazide, tolcapone, entacapone, selegiline, rasagiline, riluzole, edaravone, tetrabenazine or any combination thereof. [0030] The present disclosure also provides a use of the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure for the manufacture of a medicament. The present disclosure also provides a use of the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure for the manufacture of a medicament for the treatment of a cancer in a subject in need thereof. The present disclosure also provides a use of the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure for the manufacture of a medicament for the treatment of a neuronal disease in a subject in need thereof. [0031] The present disclosure also provides the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure for use in therapy. The present disclosure also provides the small interfering RNA, the conjugate, or the pharmaceutical composition of the present disclosure for use in therapy of a cancer in a subject in need thereof. The present disclosure also provides the small interfering RNA, the conjugate, or the composition of the present disclosure for use in therapy of a neuronal disease in a subject in need thereof. [0032] In some aspects, the cancer of the present disclosure comprises a glioblastoma, glioblastoma multiforme, colorectal cancer, hepatocytoma, hepatoma, squamous cell carcinoma, small-cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), squamous NSCLC, nonsquamous NSCLC, glioma, gastrointestinal cancer, renal cancer, clear cell carcinoma, ovarian cancer, liver cancer, endometrial cancer, kidney cancer, renal cell carcinoma (RCC), prostate cancer, hormone refractory prostate adenocarcinoma, thyroid cancer, neuroblastoma, pancreatic cancer, cervical cancer, stomach cancer, bladder cancer, breast cancer, colon carcinoma, head and neck cancer, gastric cancer, germ cell tumor, pediatric sarcoma, sinonasal natural killer, melanoma, bone cancer, skin cancer, uterine cancer, cancer of the anal region, testicular cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, rectal cancer, solid tumors of childhood, cancer of the ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain cancer, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid cancer, squamous cell cancer, environmentally-induced cancers including those induced by asbestos, virus-related cancers or cancers of viral origin (e.g., human papilloma virus (HPV-related or -originating tumors)), an IDO1 expressing cancer, or any combinations thereof. [0033] In some aspects, the neuronal disease of the present disclosure comprises Alzheimer’s disease (AD), multiple system atrophy, Parkinson’s disease (PD), Parkinson's Disease Dementia (PDD), dementia with Lewy bodies, vascular and mixed dementia, Amytrophic Lateral Sclerosis (ALS) or any combinations thereof. [0034] In some aspects, the present disclosure provides the methods, the use, or the small interfering RNAs for use in a subject in need thereof. In some aspects, the subject is a human. In some aspects, the subject is a mouse. In some aspects, the subject is a rabbit. In some aspects, the subject is a dog. In some aspects, the subject is a non-human primate. [0035] In some aspects, the present disclosure provides the methods, the use, or the small interfering RNAs for use in a subject in need thereof. In some aspects, the small interfering RNA, the conjugate, or the composition is administered orally, subcutaneously, parenterally, intrathecally, intra-cerebroventricularly, pulmonarily, topically, or intraventricularly. [0036] The present disclosure also provides a method of preparing a small interfering RNA targeting a murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript and a human indoleamine 2,3-dioxygenase 1 (IDO1) transcript at the same time comprising selecting a nucleic acid sequence within the murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript and the human indoleamine 2,3-dioxygenase 1 (IDO1) transcript and designing a contiguous nucleotide sequence of 14 to 22 nucleotides in length that is complementary to the nucleic acid sequence. In some aspects, the murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 3 and the human indoleamine 2,3-dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 1. In some aspects, the small interfering RNA comprises SEQ ID NO: 16 to SEQ ID NO: 18. In some aspects, the present disclosure provides a small interfering RNA prepared by the method of the present disclosure. [0037] The present disclosure also provides a method of preparing a small interfering RNA targeting a non-human primate indoleamine 2,3-dioxygenase 1 (IDO1) transcript and a human indoleamine 2,3-dioxygenase 1 (IDO1) transcript at the same time comprising selecting a nucleic acid sequence within the murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript and the human indoleamine 2,3-dioxygenase 1 (IDO1) transcript and designing a contiguous nucleotide sequence of 14 to 22 nucleotides in length that is complementary to the nucleic acid sequence. In some aspects, the non-human primate indoleamine 2,3- dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 13 and the human indoleamine 2,3-dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 1. In some aspects, the small interfering RNA comprises SEQ ID NO: 15. In some aspects, the present disclosure provides a small interfering RNA prepared by the method of the present disclosure. BRIEF DESCRIPTION OF THE FIGURES [0038] FIG. 1 shows human and mouse dual-target IDO1 siRNAs. Human and mouse IDO1 mRNA sequences were aligned and completely matched sequences between species 14-20 nucleotides in length with low predicted off-target effects were selected as dual- target IDO1 siRNAs. [0039] FIG. 2 shows the human IDO1 mRNA sequence. The boxes represent the target regions of the human and mouse dual-target IDO1 siRNAs as shown in FIG.1. [0040] FIG. 3 shows the mouse IDO1 mRNA sequence. The boxes represent the target regions of the human and mouse dual-target IDO1 siRNAs as shown in FIG.1. [0041] FIG. 4 shows the expression of IDO1 protein in HeLa cells after treatment with different siRNAs targeting IDO1 mRNA as measured using Western blot analysis. HeLa cells were plated at 3.5 x 10⁴ cells/well in 24-well plates and incubated overnight with complete DMEM medium. The wells were treated with 20 to 100 nM of siIDO1-1 to siIDO1-4 with 0.1 to 0.25 μL of RNAiMAX for 6 h. After replacement with fresh complete DMEM medium containing IFN- γ (5 ng/ml), the cells were incubated for an additional 48 h. A mix of non-functional siRNAs was used as a negative control (NC) and siRNAs targeting IDO1 were used as positive controls (PC-1: GUCUAGUCUGGGAUGCAUtt (SEQ ID NO: 19) and PC-2: CUGAGUUGGCCUUAGUGUAtt (SEQ ID NO: 20)). NT is “not treated.” Both negative and positive controls were purchased from Bioneer, Korea. After 48 h, the cells were harvested for Western blot analysis. FIG. 4 shows the IDO1 protein level of HeLa cells after treatment with IDO1 siRNAs. [0042] FIG. 5 shows the expression of IDO1 protein in HeLa cells after treatment with different low concentrations of IDO1 siRNAs as measured using Western blot. HeLa cells were cultured at 3.5 x 10⁴ cells/well in 24-well plates and incubated overnight with complete DMEM medium. The wells were treated with 10 to 20 nM of siIDO1-1 to siIDO1- 4 with 0.1 μL of RNAiMAX for 6 h. After replacement with fresh complete DMEM medium containing IFN-γ (5 ng/ml), the cells were incubated for an additional 48 h. No treatment (NT) was used as a negative control and indicates no treatment with IFN- γ.After 48 h, the cells were harvested for Western blot analysis. DETAILED DESCRIPTION OF DISCLOSURE [0043] The present application is generally directed to oligonucleotides, e.g., siRNAs, that are capable of specifically binding to a region within an IDO1 transcript. Specifically, as demonstrated herein, the oligonucleotides, e.g., siRNAs, described herein are capable of specifically binding to IDO1 transcripts from variety of species, e.g., human, mouse, rabbit, dog, and/or non-human primate. Accordingly, the oligonucleotides, e.g., siRNAs, described herein can be useful in regulating IDO1 expression in variety of subjects. Additionally, as also demonstrated herein, the specific binding of the oligonucleotides, e.g., siRNAs, to a region within the IDO1 transcript can reduce or inhibit the expression of the encoded IDO1 protein. Accordingly, the oligonucleotides, e.g., siRNAs, described herein can also be used to treat a wide range of diseases and disorders, including those associated with abnormal IDO1 expression. Additional aspects of the present disclosure are provided throughout the present application. [0044] To facilitate an understanding of the disclosure provided herein, a number of terms and phrases are defined. Additional definitions are set forth throughout the detailed description. I. Definitions [0045] It is to be noted that the term "a" or "an" entity refers to one or more of that entity; for example, "a nucleotide sequence," is understood to represent one or more nucleotide sequences. As such, the terms "a" (or "an"), "one or more," and "at least one" can be used interchangeably herein. [0046] Furthermore, "and/or" where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term "and/or" as used in a phrase such as "A and/or B" herein is intended to include "A and B," "A or B," "A" (alone), and "B" (alone). Likewise, the term "and/or" as used in a phrase such as "A, B, and/or C" is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone). [0047] It is understood that wherever aspects are described herein with the language "comprising," otherwise analogous aspects described in terms of "consisting of" and/or "consisting essentially of" are also provided. [0048] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure is related. For example, the Concise Dictionary of Biomedicine and Molecular Biology, Juo, Pei-Show, 2nd ed., 2002, CRC Press; The Dictionary of Cell and Molecular Biology, 3rd ed., 1999, Academic Press; and the Oxford Dictionary Of Biochemistry And Molecular Biology, Revised, 2000, Oxford University Press, provide one of skill with a general dictionary of many of the terms used in this disclosure. [0049] Units, prefixes, and symbols are denoted in their Système International de Unites (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range. Unless otherwise indicated, nucleotide sequences are written left to right in 5' to 3' orientation. Amino acid sequences are written left to right in amino to carboxy orientation. The headings provided herein are not limitations of the various aspects of the disclosure, which can be had by reference to the specification as a whole. Accordingly, the terms defined immediately below are more fully defined by reference to the specification in its entirety. [0050] The term "about" is used herein to mean approximately, roughly, around, or in the regions of. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term "about" can modify a numerical value above and below the stated value by a variance of, e.g., 10 percent, up or down (higher or lower). For example, if it is stated that "the siRNA reduces expression of IDO1 protein in a cell following administration of the siRNA by at least about 60%," it is implied that the IDO1 levels are reduced by a range of 50% to 70%. [0051] The term "small interfering RNA" (siRNA) refers to an oligomer or polymer of nucleosides, such as naturally-occurring nucleosides or modified forms thereof, that are covalently linked to each other through internucleotide linkages. The siRNA can include at least one non-naturally occurring nucleoside. An siRNA is complementary to a target nucleic acid, such that the siRNA hybridizes to the target nucleic acid sequence. The terms "antisense siRNA," "siRNA," and "oligomer" as used herein are interchangeable with the term "siRNA." [0052] The term "nucleic acids" or "nucleotides" is intended to encompass plural nucleic acids. In some aspects, the term "nucleic acids" or "nucleotides" refers to a target sequence, e.g., pre-mRNAs, mRNAs, or DNAs in vivo or in vitro. When the term refers to the nucleic acids or nucleotides in a target sequence, the nucleic acids or nucleotides can be naturally occurring sequences within a cell. In some aspects, "nucleic acids" or "nucleotides" refer to a sequence in the siRNAs of the disclosure. When the term refers to a sequence in the siRNAs, the nucleic acids or nucleotides are not naturally occurring, i.e., chemically synthesized, enzymatically produced, recombinantly produced, or any combination thereof. In one aspect, the nucleic acids or nucleotides in the siRNAs are produced synthetically or recombinantly, but are not a naturally occurring sequence or a fragment thereof. In one aspect, the nucleic acids or nucleotides in the siRNAs are not naturally occurring because they contain at least one nucleotide analog that is not naturally occurring in nature. The term "nucleic acid" or "nucleoside" refers to a single nucleic acid segment, e.g., a DNA, an RNA, or an analog thereof, present in a polynucleotide. "Nucleic acid" or "nucleoside" includes naturally occurring nucleic acids or non-naturally occurring nucleic acids. In some aspects, the terms "nucleotide", "unit" and "monomer" are used interchangeably. It will be recognized that when referring to a sequence of nucleotides or monomers, what is referred to is the sequence of bases, such as A, T, G, C or U, and analogs thereof. [0053] The term "nucleotide" as used herein, refers to a glycoside comprising a sugar moiety, a base moiety and a covalently linked group (linkage group), such as a phosphate or phosphorothioate internucleotide linkage group, and covers both naturally occurring nucleotides, such as DNA or RNA, and non-naturally occurring nucleotides comprising modified sugar and/or base, which are also referred to as "nucleotide analogs" herein. Herein, a single nucleotide (unit) can also be referred to as a monomer or nucleic acid unit. In some aspects, the term "nucleotide analogs" refers to nucleotides having modified sugar moieties. Non-limiting examples of the nucleotides having modified sugar moieties (e.g., LNA) are disclosed elsewhere herein. In some aspects, the term "nucleotide analogs" refers to nucleotides having modified nucleobase moieties. The nucleotides having modified nucleobase moieties include, but are not limited to, 5-methylcytosine, isocytosine, pseudoisocytosine, 5-bromouracil, 5-propynyluracil, 6-aminopurine, 2-aminopurine, inosine, diaminopurine, and 2-chloro-6-aminopurine. [0054] The term "nucleoside" as used herein is used to refer to a glycoside comprising a sugar moiety and a base moiety, which can be covalently linked by the internucleotide linkages between the nucleosides of the siRNA. In the field of biotechnology, the term "nucleoside" is often used to refer to a nucleic acid monomer or unit. In the context of an siRNA, the term "nucleoside" can refer to the base alone, i.e., a nucleobase sequence comprising cytosine (DNA and RNA), guanine (DNA and RNA), adenine (DNA and RNA), thymine (DNA) and uracil (RNA), in which the presence of the sugar backbone and internucleotide linkages are implicit. Likewise, particularly in the case of oligonucleotides where one or more of the internucleotide linkage groups are modified, the term "nucleotide" can refer to a "nucleoside." For example the term "nucleotide" can be used, even when specifying the presence or nature of the linkages between the nucleosides. [0055] The term "nucleotide length" as used herein means the total number of the nucleotides (monomers) in a given sequence. For example, the sequence of GTCCGTAAGGTCTTGCCAA (SEQ ID NO: 15) has 19 nucleotides; thus the nucleotide length of the sequence is 19. The term "nucleotide length" is therefore used herein interchangeably with "nucleotide number." [0056] As one of ordinary skill in the art would recognize, the 5' terminal nucleotide of an oligonucleotide does not comprise a 5' internucleotide linkage group, although it can comprise a 5' terminal group. [0057] As used herein, a "coding region" or "coding sequence" is a portion of polynucleotide which consists of codons translatable into amino acids. Although a "stop codon" (TAG, TGA, or TAA) is typically not translated into an amino acid, it can be considered to be part of a coding region, but any flanking sequences, for example promoters, ribosome binding sites, transcriptional terminators, introns, untranslated regions ("UTRs"), and the like, are not part of a coding region. The boundaries of a coding region are typically determined by a start codon at the 5' terminus, encoding the amino terminus of the resultant polypeptide, and a translation stop codon at the 3' terminus, encoding the carboxyl terminus of the resulting polypeptide. [0058] The term "non-coding region" as used herein means a nucleotide sequence that is not a coding region. Examples of non-coding regions include, but are not limited to, promoters, ribosome binding sites, transcriptional terminators, introns, untranslated regions ("UTRs"), non-coding exons and the like. Some of the exons can be wholly or part of the 5' untranslated region (5' UTR) or the 3' untranslated region (3' UTR) of each transcript. The untranslated regions are important for efficient translation of the transcript and for controlling the rate of translation and half-life of the transcript. [0059] The term "region" when used in the context of a nucleotide sequence refers to a section of that sequence. For example, the phrase "region within a nucleotide sequence" or "region within the complement of a nucleotide sequence" refers to a sequence shorter than the nucleotide sequence, but longer than at least 10 nucleotides located within the particular nucleotide sequence or the complement of the nucleotides sequence, respectively. The term "sub-sequence" or "subsequence" can also refer to a region of a nucleotide sequence. [0060] The term "downstream," when referring to a nucleotide sequence, means that a nucleic acid or a nucleotide sequence is located 3' to a reference nucleotide sequence. In some aspects, downstream nucleotide sequences relate to sequences that follow the starting point of transcription. For example, the translation initiation codon of a gene is located downstream of the start site of transcription. [0061] The term "upstream" refers to a nucleotide sequence that is located 5' to a reference nucleotide sequence. [0062] Unless otherwise indicated, the sequences provided herein are listed from 5' end (left) to 3' end (right). [0063] As used herein, the term "regulatory region" refers to nucleotide sequences located upstream (5' non-coding sequences), within, or downstream (3' non-coding sequences) of a coding region, and which influence the transcription, RNA processing, stability, or translation of the associated coding region. Regulatory regions can include promoters, translation leader sequences, introns, polyadenylation recognition sequences, RNA processing sites, effector binding sites, UTRs, and stem-loop structures. If a coding region is intended for expression in a eukaryotic cell, a polyadenylation signal and transcription termination sequence will usually be located 3' to the coding sequence. [0064] The term "transcript" as used herein can refer to a primary transcript that is synthesized by transcription of DNA and becomes a messenger RNA (mRNA) after processing, i.e., a precursor messenger RNA (pre-mRNA), and the processed mRNA itself. The term "transcript" can be interchangeably used with "pre-mRNA" and "mRNA." After DNA strands are transcribed to primary transcripts, the newly synthesized primary transcripts are modified in several ways to be converted to their mature, functional forms such as mRNA, tRNA, rRNA, lncRNA, miRNA and others. Thus, the term "transcript" can include exons, introns, 5' UTRs, and 3' UTRs. [0065] The term "expression" as used herein refers to a process by which a polynucleotide produces a gene product, for example, a RNA or a polypeptide. It includes, without limitation, transcription of the polynucleotide into messenger RNA (mRNA) and the translation of an mRNA into a polypeptide. Expression produces a "gene product." As used herein, a gene product can be either a nucleic acid, e.g., a messenger RNA produced by transcription of a gene, or a polypeptide which is translated from a transcript. Gene products described herein further include nucleic acids with post transcriptional modifications, e.g., polyadenylation or splicing, or polypeptides with post translational modifications, e.g., methylation, glycosylation, the addition of lipids, association with other protein subunits, or proteolytic cleavage. [0066] As used herein and unless indicated otherwise, the term "inhibit" (and derivatives thereof) comprises both complete inhibition and partial inhibition. Accordingly, in some aspects, an siRNA described herein is capable of completely inhibiting the expression of an IDO1 mRNA and/or IDO1 protein, such that a cell exhibits no expression of the IDO1 mRNA and/or IDO1 protein. In some aspects, an siRNA described herein is capable of partially inhibiting the expression of an IDO1 mRNA and/or IDO1 protein, such that a cell exhibits reduced expression of the IDO1 mRNA and/or IDO1 protein as compared to a corresponding cell that was not treated or contacted with an siRNA described herein. For instance, in some aspects, expression of an IDO1 mRNA and/or IDO1 protein is partially reduced, wherein the expression is reduced by at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or about 99% as compared a corresponding cell that was not treated or contacted with an siRNA described herein. Accordingly, the terms "inhibit" and "reduce" (and derivatives thereof) are used herein interchangeably. [0067] The terms "identical" or percent "identity" in the context of two or more nucleic acids refer to two or more sequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned (introducing gaps, if necessary) for maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity. The percent identity can be measured using sequence comparison software or algorithms or by visual inspection. Various algorithms and software are known in the art that can be used to obtain alignments of amino acid or nucleotide sequences. [0068] One such non-limiting example of a sequence alignment algorithm is the algorithm described in Karlin et al., 1990, Proc. Natl. Acad. Sci., 87:2264-2268, as modified in Karlin et al., 1993, Proc. Natl. Acad. Sci., 90:5873-5877, and incorporated into the NBLAST and XBLAST programs (Altschul et al., 1991, Nucleic Acids Res., 25:3389-3402). In some aspects, Gapped BLAST can be used as described in Altschul et al., 1997, Nucleic Acids Res. 25:3389-3402. BLAST-2, WU-BLAST-2 (Altschul et al., 1996, Methods in Enzymology, 266:460-480), ALIGN, ALIGN-2 (Genentech, South San Francisco, California) or Megalign (DNASTAR) are additional publicly available software programs that can be used to align sequences. In some aspects, the percent identity between two nucleotide sequences is determined using the GAP program in the GCG software package (e.g., using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 90 and a length weight of 1, 2, 3, 4, 5, or 6). In some aspects, the GAP program in the GCG software package, which incorporates the algorithm of Needleman and Wunsch (J. Mol. Biol. (48):444-453 (1970)) can be used to determine the percent identity between two amino acid sequences (e.g., using either a BLOSUM 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5). Alternatively, in some aspects, the percent identity between nucleotide or amino acid sequences is determined using the algorithm of Myers and Miller (CABIOS, 4:11-17 (1989)). For example, the percent identity can be determined using the ALIGN program (version 2.0) and using a PAM120 with residue table, a gap length penalty of 12 and a gap penalty of 4. One skilled in the art can determine appropriate parameters for maximal alignment by particular alignment software. In some aspects, the default parameters of the alignment software are used. [0069] In some aspects, the percentage identity "X" of a first nucleotide sequence to a second nucleotide sequence is calculated as 100 x (Y/Z), where Y is the number of amino acid residues scored as identical matches in the alignment of the first and second sequences (as aligned by visual inspection or a particular sequence alignment program) and Z is the total number of residues in the second sequence. If the length of a first sequence is longer than the second sequence, the percent identity of the first sequence to the second sequence will be higher than the percent identity of the second sequence to the first sequence. [0070] Different regions within a single polynucleotide target sequence that align with a polynucleotide reference sequence can each have their own percent sequence identity. It is noted that the percent sequence identity value is rounded to the nearest tenth. For example, 80.11, 80.12, 80.13, and 80.14 are rounded down to 80.1, while 80.15, 80.16, 80.17, 80.18, and 80.19 are rounded up to 80.2. It also is noted that the length value will always be an integer. [0071] As used herein, the terms "homologous" and "homology" are interchangeable with the terms "identity" and "identical." [0072] The term "naturally occurring variant thereof" refers to variants of the IDO1 polypeptide sequence or IDO1 nucleic acid sequence (e.g., transcript) which exist naturally within the defined taxonomic group, such as mammalian, such as mouse, dog, rabbit, non- human primate, and human. Typically, when referring to "naturally occurring variants" of a polynucleotide the term also can encompass any allelic variant of the IDO1 -encoding genomic DNA by chromosomal translocation or duplication, and the RNA, such as mRNA derived therefrom. "Naturally occurring variants" can also include variants derived from alternative splicing of the IDO1 mRNA. When referenced to a specific polypeptide sequence, e.g., the term also includes naturally occurring forms of the protein, which can therefore be processed, e.g., by co- or post-translational modifications, such as signal peptide cleavage, proteolytic cleavage, glycosylation, etc. [0073] In determining the degree of "complementarity" between siRNAs of the disclosure (or regions thereof) and the target region of the nucleic acid which encodes mammalian IDO1 protein (e.g., the IDO1 gene), such as those disclosed herein, the degree of "complementarity" (also, "homology" or "identity") is expressed as the percentage identity (or percentage homology) between the sequence of the siRNA (or region thereof) and the sequence of the target region (or the reverse complement of the target region) that best aligns therewith. The percentage is calculated by counting the number of aligned bases that are identical between the two sequences, dividing by the total number of contiguous monomers in the siRNA, and multiplying by 100. In such a comparison, if gaps exist, it is preferable that such gaps are merely mismatches rather than areas where the number of monomers within the gap differs between the siRNA of the disclosure and the target region. [0074] The term "complement" as used herein indicates a sequence that is complementary to a reference sequence. It is well known that complementarity is the base principle of DNA replication and transcription as it is a property shared between two DNA or RNA sequences, such that when they are aligned antiparallel to each other, the nucleotide bases at each position in the sequences will be complementary, much like looking in the mirror and seeing the reverse of things. Therefore, for example, the complement of a sequence of 5’"ATGC"3’ can be written as 3’"TACG"5’ or 5’"GCAT"3’. The terms "reverse complement", "reverse complementary" and "reverse complementarity" as used herein are interchangeable with the terms "complement", "complementary" and "complementarity." [0075] The terms "corresponding to" and "corresponds to," when referencing two separate nucleic acid or nucleotide sequences can be used to clarify regions of the sequences that correspond or are similar to each other based on homology and/or functionality, although the nucleotides of the specific sequences can be numbered differently. For example, different isoforms of a gene transcript can have similar or conserved portions of nucleotide sequences whose numbering can differ in the respective isoforms based on alternative splicing and/or other modifications. In addition, it is recognized that different numbering systems can be employed when characterizing a nucleic acid or nucleotide sequence (e.g., a gene transcript and whether to begin numbering the sequence from the translation start codon or to include the 5'UTR). Further, it is recognized that the nucleic acid or nucleotide sequence of different variants of a gene or gene transcript can vary. As used herein, however, the regions of the variants that share nucleic acid or nucleotide sequence homology and/or functionality are deemed to "correspond" to one another. For example, a nucleotide sequence of a IDO1 transcript corresponding to nucleotides X to Y of SEQ ID NO: 1 ("reference sequence") refers to an IDO1 transcript sequence (e.g., IDO1 mRNA) that has an identical sequence or a similar sequence to nucleotides X to Y of SEQ ID NO: 1. A person of ordinary skill in the art can identify the corresponding X and Y residues in the IDO1 transcript sequence by aligning the IDO1 transcript sequence with SEQ ID NO: 1. [0076] The terms "corresponding nucleotide analog" and "corresponding nucleotide" are intended to indicate that the nucleobase in the nucleotide analog and the naturally occurring nucleotide have the same pairing, or hybridizing, ability. For example, when the 2- deoxyribose unit of the nucleotide is linked to an adenine, the "corresponding nucleotide analog" contains a pentose unit (different from 2-deoxyribose) linked to an adenine. [0077] The term "siRNA Number" or "siRNA No." as used herein refers to a unique number given to a nucleotide sequence. For example, siRNA-1 refers to GTCCGTAAGGTCTTGCCAA (SEQ ID NO: 15). [0078] "Potency" is normally expressed as an IC50 or EC50 value, in µM, nM or pM unless otherwise stated. Potency can also be expressed in terms of percent inhibition. IC50 is the median inhibitory concentration of a therapeutic molecule. EC₅₀ is the median effective concentration of a therapeutic molecule relative to a vehicle or control (e.g., saline). In functional assays, IC50 is the concentration of a therapeutic molecule that reduces a biological response, e.g., transcription of mRNA or protein expression, by 50% of the biological response that is achieved by the therapeutic molecule. In functional assays, EC₅₀ is the concentration of a therapeutic molecule that produces 50% of the biological response, e.g., transcription of mRNA or protein expression. IC₅₀ or EC₅₀ can be calculated by any number of means known in the art. [0079] The term “tumor,” as used herein, includes reference to cellular material, e.g., a tissue, proliferating at an abnormally high rate. A growth comprising neoplastic cells is a neoplasm, also known as a “tumor,” and generally forms a distinct tissue mass in a body of a subject. A tumor can show partial or total lack of structural organization and functional coordination with the normal tissue. As used herein, a tumor is intended to encompass hematopoietic tumors as well as solid tumors. In some aspects, the tumor is a solid tumor. The term “tumor,” as used herein, includes reference to the tumor micro-environment or tumor site, i.e., the area within the tumor and the area directly outside the tumorous tissue. In some aspects, the tumor micro-environment or tumor site includes an area within the boundaries of the tumor tissue. In some aspects, the tumor micro-environment or tumor site includes the tumor interstitial compartment of a tumor, which is defined herein as all that is interposed between the plasma membrane of neoplastic cells and the vascular wall of the newly formed neovessels. As used herein, the terms “tumor micro-environment” or “tumor site” refers to a location within a subject in which a tumor resides, including the area immediately surrounding the tumor. As used herein, “cells of the tumor micro- environment” include any cells that are present in the tumor micro-environment, including, but not limited to tumor cells and immune cells. [0080] By "subject" or "individual" or "animal" or "patient" or "mammal," is meant any subject, particularly a mammalian subject, for whom diagnosis, prognosis, or therapy is desired. Mammalian subjects include humans, domestic animals, farm animals, sports animals, and zoo animals including, e.g., humans, non-human primates, dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, bears, and so on. [0081] The term "pharmaceutical composition" refers to a preparation which is in such form as to permit the biological activity of the active ingredient to be effective, and which contains no additional components which are unacceptably toxic to a subject to which the composition would be administered. Such composition can be sterile. [0082] An "effective amount" of an siRNA as disclosed herein is an amount sufficient to carry out a specifically stated purpose. An "effective amount" can be determined empirically and in a routine manner, in relation to the stated purpose. [0083] Terms such as "treating" or "treatment" or "to treat" or "alleviating" or "to alleviate" refer to both (1) therapeutic measures that cure, slow down, lessen symptoms of, and/or halt progression of a diagnosed pathologic condition or disorder and (2) prophylactic or preventative measures that prevent and/or slow the development of a targeted pathologic condition or disorder. Thus, those in need of treatment include those already with the disorder; those prone to have the disorder; and those in whom the disorder is to be prevented. In some aspects, a subject is successfully "treated" for a disease or condition disclosed elsewhere herein according to the methods provided herein if the patient shows, e.g., total, partial, or transient alleviation or elimination of symptoms associated with the disease or disorder. II. Oligonucleotides, e.g., Small interfering RNAs [0084] Some aspects of the present disclosure relates to oligonucleotides, e.g., small interfering RNAs (siRNAs), that can be used to modulate the function of nucleic acid molecules encoding mammalian IDO1, such as the IDO1 nucleic acid, e.g., IDO1 transcript, including IDO1 pre-mRNA, and IDO1 mRNA, or naturally occurring variants of such nucleic acid molecules encoding mammalian IDO1. As demonstrated and further described herein, the oligonucleotides, e.g., siRNAs, provided herein are capable of specifically binding to a region within an IDO1 transcript and thereby, inhibit the expression of the encoded IDO1 protein in a cell. [0085] In various aspects, the oligonucleotide, e.g., siRNA, of the disclosure does not comprise RNA (units). In some aspects, the oligonucleotide, e.g., siRNA, comprises one or more DNA units. In one aspect, the oligonucleotide, e.g., siRNA, according to the disclosure is a linear molecule or is synthesized as a linear molecule. In some aspects, the oligonucleotide, e.g., siRNA, is a double stranded molecule. In some aspects, the oligonucleotide, e.g., siRNA, is not a single stranded molecule. In some aspects, the oligonucleotide, e.g., siRNA, is not an antisense oligonucleotide (ASO). In various aspects, the oligonucleotide, e.g., siRNA, of the disclosure can consist entirely of the contiguous nucleotide region. [0086] In one aspect, the oligonucleotide, e.g., siRNA, of the disclosure can be in the form of any pharmaceutically acceptable salts. The term "pharmaceutically acceptable salts" as used herein refers to derivatives of the oligonucleotide, e.g., siRNA, of the disclosure wherein the oligonucleotide, e.g., siRNA, is modified (e.g., addition of a cation) by making salts thereof. Such salts retain the desired biological activity of the oligonucleotides, e.g., siRNAs, without imparting undesired toxicological effects. In some aspects, the oligonucleotide, e.g., siRNA, of the disclosure is in the form of a sodium salt. In some aspects, the oligonucleotide, e.g., siRNA, is in the form of a potassium salt. Additional aspects of the oligonucleotides, e.g., siRNAs, useful for the present disclosure are provided below in more detail. II.A. The Target [0087] Suitably, the oligonucleotide, e.g., siRNA, of the disclosure is capable of down- regulating and/or inhibiting the expression of an IDO1 protein in a cell. In this regard, the oligonucleotide, e.g., siRNA, of the disclosure can affect indirect inhibition of IDO1 protein through the reduction in IDO1 mRNA levels in a variety of cell types, including those from multiple species (e.g., humans, mice, rabbits, dogs, and/or non-human primates), Accordingly, in some aspects,, the present disclosure is directed to siRNAs that target one or more regions (also referred to herein as a "target region") of the IDO1 mRNA. [0088] Synonyms of IDO1 are known and include indoleamine 2,3-dioxygenase 1, IDO, IDO-1, and INDO. [0089] The sequence for the Homo sapiens (human) IDO1 gene can be found under publicly available Accession Numbers NC_000008.11 and NC_060932.1. The sequence for human IDO1 mRNA can be found under publicly available Accession Number: NM_002164.6 (SEQ ID NO: 1) which is incorporated by reference herein in its entirety. The sequence for human IDO1 protein can be found under publicly available Accession Number: NP_002155.1 (SEQ ID NO: 2) which is incorporated by reference herein in its entirety. [0090] The sequence for the Mus musculus (mouse) IDO1 gene can be found under publicly available Accession Number: NC_000074.7. The sequences for mouse IDO1 mRNAs can be found under publicly available Accession Numbers: NM_008324.2 (SEQ ID NO: 3) and NM_001293690.1 (SEQ ID NO: 5) which are each incorporated by reference herein in its entirety. The sequence for mouse IDO1 protein can be found under publicly available Accession Numbers: NP_032350.1 (SEQ ID NO: 4) and NP_001280619.1 (SEQ ID NO: 6) which are each incorporated by reference herein in their entirety. [0091] The sequence for the Oryctolagus cuniculus (rabbit) IDO1 gene can be found under publicly available Accession Number: NW_003159332.1. The sequences for rabbit IDO1 mRNAs can be found under publicly available Accession Numbers: XM_002720800.3 (SEQ ID NO: 7) and XM_008273932.2 (SEQ ID NO: 9) which are each incorporated by reference herein in its entirety. The sequence for rabbit IDO1 protein can be found under publicly available Accession Numbers: XP_002720846.1 (SEQ ID NO: 8) and XP_008272154.1 (SEQ ID NO: 10) which are each incorporated by reference herein in their entirety. [0092] The sequence for the Canis lupus familiaris (dog) IDO1 gene can be found under publicly available Accession Numbers: NC_051820.1, NC_006598.4, NC_049237.1, NC_049276.1, and NC_049757.1. The sequences for dog IDO1 mRNAs can be found under publicly available Accession Numbers: XM_038689794.1 (SEQ ID NO: 11), XM_038497541.1, XM_038624035.1, XM_038560004.1, and XM_532793.7 which are each incorporated by reference herein in its entirety. The sequences for dog IDO1 proteins can be found under publicly available Accession Numbers: XP_038545722.1 (SEQ ID NO: 12), XP_038353469.1, XP_038479963.1, XP_038415932.1, XP_532793.1 which are each incorporated by reference herein in their entirety. [0093] The sequence for the Macaca mulatta (rhesus macaque) IDO1 gene can be found under publicly available Accession Number: NC_041761.1. The sequence for rhesus macaque IDO1 mRNA can be found under publicly available Accession Numbers: NM_001077483.1 (SEQ ID NO: 13) which is incorporated by reference herein in its entirety. The sequence for rhesus macaque IDO1 proteins can be found under publicly available Accession Numbers: NP_001070951.1 (SEQ ID NO: 14 which is incorporated by reference herein in its entirety. [0094] Suitably, in some aspects, the oligonucleotides, e.g., siRNAs, of the present disclosure is prepared by any suitable methods known in the art. For instance, in some aspects, in preparing an oligonucleotide, e.g., siRNA, that is capable of targeting both a murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript and a human indoleamine 2,3- dioxygenase 1 (IDO1) transcript, the method comprises selecting a nucleic acid sequence within the murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript and the human indoleamine 2,3-dioxygenase 1 (IDO1) transcript and designing a contiguous nucleotide sequence of 10 to 50 nucleotides in legnth, e.g., 10 to 30 nucleotides in length, e.g., 14 to 22 nucleotides in length, that is complementary to the nucleic acid sequence. In some aspects, the siRNA is 10 to 25 nucleotides in length. In some aspects, the murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 3 and the human indoleamine 2,3-dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 1. In some aspects, in preparing an oligonucleotide, e.g., siRNA, that is capable of targeting a non- human primate indoleamine 2,3-dioxygenase 1 (IDO1) transcript and a human indoleamine 2,3-dioxygenase 1 (IDO1) transcript, the method comprises selecting a nucleic acid sequence within the murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript and the human indoleamine 2,3-dioxygenase 1 (IDO1) transcript and designing a contiguous nucleotide sequence of 14 to 22 nucleotides in length that is complementary to the nucleic acid sequence. In some aspects, the non-human primate indoleamine 2,3-dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 13 and the human indoleamine 2,3-dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 1. [0095] Therefore, as is apparent from the present disclosure the oligonucleotides, e.g., siRNAs, of the present disclosure are capable of inhibiting the expression of an IDO1 protein, including any variants thereof, in multiple species, e.g., by specifically binding to a mRNA encoding the protein which is reduced. [0096] In some aspects, an oligonucleotide, e.g., siRNA, described herein is capable of specifically binding to a region within a human IDO1 target nucleic acid sequence. An example of such a target nucleic acid sequence is human IDO1 mRNA. SEQ ID NO: 1 in FIG. 2 represents the human IDO1 mRNA sequence. Accordingly, in some aspects, siRNAs described herein comprise a contiguous nucleotide sequence that is capable of specifically binding to a region within the human IDO1 mRNA sequence set forth in SEQ ID NO: 1. More specifically, in some aspects, provided herein is an oligonucleotide, e.g., siRNA, comprising a continugous nucleotide sequence of about 10 to about 30 (e.g., about 14 to 25, e.g., about 14 to about 22) nucleotides in length, wherein the contiguous nucleotide sequence is complementary to a target region within SEQ ID NO: 1. In some aspects, the target region corresponds to nucleotides 811-829 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 811-829 of SEQ ID NO: 1 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 811-829 of SEQ ID NO: 1. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 811-829 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 811-829 of SEQ ID NO: 1 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 811-829 of SEQ ID NO: 1. [0097] In some aspects, the target region corresponds to nucleotides 327-345 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 327-345 of SEQ ID NO: 1 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 327-345 of SEQ ID NO: 1. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 327-345 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 327-345 of SEQ ID NO: 1 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 327-345 of SEQ ID NO: 1. [0098] In some aspects, the target region corresponds to nucleotides 425-442 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 425-442 of SEQ ID NO: 1 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 425-442 of SEQ ID NO: 1. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 425-442 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 425-442 of SEQ ID NO: 1 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 425-442 of SEQ ID NO: 1. [0099] In some aspects, the target region corresponds to nucleotides 528-546 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 528-546 of SEQ ID NO: 1 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 528-546 of SEQ ID NO: 1. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 528-546 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 528-546 of SEQ ID NO: 1 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 528-546 of SEQ ID NO: 1. [0100] In some aspects, an oligonucleotide, e.g., siRNA, described herein is capable of specifically binding to a region within a mouse IDO1 targeting nucleic acid sequence. SEQ ID NO: 3 in FIG. 3 represents a mouse IDO1 mRNA sequence. Accordingly, in some aspects, siRNAs described herein comprise a contiguous nucleotide sequence that is capable of specifically binding to a region within the mouse IDO1 mRNA sequence set forth in SEQ ID NO: 3. More specifically, in some aspects, provided herein is an oligonucleotide, e.g., siRNA, comprising a continugous nucleotide sequence of about 10 to about 30 (e.g., about 14 to about 22) nucleotides in length, wherein the contiguous nucleotide sequence is complementary to a region within SEQ ID NO: 3. In some aspects, the target region corresponds to nucleotides 804-822 of SEQ ID NO: 3 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 804-822 of SEQ ID NO: 3 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the region corresponds to nucleotides 804- 822 of SEQ ID NO: 3. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 804- 822 of SEQ ID NO: 3 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 804-822 of SEQ ID NO: 3 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 804-822 of SEQ ID NO: 3. [0101] In some aspects, the target region corresponds to nucleotides 418-435 of SEQ ID NO: 3 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 418-435 of SEQ ID NO: 3 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the region corresponds to nucleotides 418-435 of SEQ ID NO: 3. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 418-435 of SEQ ID NO: 3 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 418-435 of SEQ ID NO: 3 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 418-435 of SEQ ID NO: 3. [0102] In some aspects, the target region corresponds to nucleotides 521-539 of SEQ ID NO: 3 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 521-539 of SEQ ID NO: 3 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the region corresponds to nucleotides 521-539 of SEQ ID NO: 3. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 521-539 of SEQ ID NO: 3 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 521-539 of SEQ ID NO: 3 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 521-539 of SEQ ID NO: 3. [0103] In some aspects, an oligonucleotide, e.g., siRNA, described herein is capable of specifically binding to a region within the sequence set forth in SEQ ID NO: 5, which is another mouse IDO1 targeting nucleic acid sequence. Accordingly, in some aspects, siRNAs described herein comprise a contiguous nucleotide sequence that is capable of specifically binding to a region within the mouse IDO1 mRNA sequence set forth in SEQ ID NO: 5. More specifically, in some aspects, provided herein is an oligonucleotide, e.g., siRNA, comprising a continugous nucleotide sequence of about 10 to about 30 (e.g., about 14 to about 22) nucleotides in length, wherein the contiguous nucleotide sequence is complementary to a region within SEQ ID NO: 5. In some aspects, the target region corresponds to nucleotides 957-975 of SEQ ID NO: 5 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 957-975 of SEQ ID NO: 5 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the region corresponds to nucleotides 957-975 of SEQ ID NO: 5. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 957-975 of SEQ ID NO: 5 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 957-975 of SEQ ID NO: 5 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 957-975 of SEQ ID NO: 5. [0104] In some aspects, the target region corresponds to nucleotides 571-588 of SEQ ID NO: 5 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 571-588 of SEQ ID NO: 5 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the region corresponds to nucleotides 571-588 of SEQ ID NO: 5. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 571-588 of SEQ ID NO: 5 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 571-588 of SEQ ID NO: 5 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 571-588 of SEQ ID NO: 5. [0105] In some aspects, the target region corresponds to nucleotides 674-692 of SEQ ID NO: 5 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 674-692 of SEQ ID NO: 5 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the region corresponds to nucleotides 674-692 of SEQ ID NO: 5. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 674-692 of SEQ ID NO: 5 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 674-692 of SEQ ID NO: 5 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 674-692 of SEQ ID NO: 5. [0106] In some aspects, an oligonucleotide, e.g., siRNA, described herein is capable of specifically binding to a region within a rabbit IDO1 targeting nucleic acid sequence. An example of such a target nucleic acid sequence is the rabbit IDO1 mRNA sequence set forth in SEQ ID NO: 7. Accordingly, in some aspects, siRNAs described herein comprise a contiguous nucleotide sequence that is capable of specifically binding to a region within the rabbit IDO1 mRNA sequence set forth in SEQ ID NO: 7. More specifically, in some aspects, provided herein is an oligonucleotide, e.g., siRNA, comprising a continugous nucleotide sequence of about 10 to about 30 (e.g., about 14 to about 22) nucleotides in length, wherein the contiguous nucleotide sequence is complementary to a region within SEQ ID NO: 7. In some aspects, the target region corresponds to nucleotides 463-480 of SEQ ID NO: 7 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 463-480 of SEQ ID NO: 7 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the region corresponds to nucleotides 463-480 of SEQ ID NO: 7. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 463-480 of SEQ ID NO: 7 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 463-480 of SEQ ID NO: 7 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 463-480 of SEQ ID NO: 7. [0107] In some aspects, an oligonucleotide, e.g., siRNA, described herein is capable of specifically binding to a region within a rabbit IDO1 targeting nucleic acid sequence. An example of such a target nucleic acid sequence is the rabbit IDO1 mRNA sequence set forth in SEQ ID NO: 9. Accordingly, in some aspects, siRNAs described herein comprise a contiguous nucleotide sequence that is capable of specifically binding to a region within the rabbit IDO1 mRNA sequence set forth in SEQ ID NO: 9. More specifically, in some aspects, provided herein is an oligonucleotide, e.g., siRNA, comprising a continugous nucleotide sequence of about 10 to about 30 (e.g., about 14 to about 22) nucleotides in length, wherein the contiguous nucleotide sequence is complementary to a region within SEQ ID NO: 9. In some aspects, the target region corresponds to nucleotides 570-587 of SEQ ID NO: 9 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 570-587 of SEQ ID NO: 9 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the region corresponds to nucleotides 570-587 of SEQ ID NO: 9. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 570-587 of SEQ ID NO: 9 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 570-587 of SEQ ID NO: 9 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 570-587 of SEQ ID NO: 9. [0108] In some aspects, an oligonucleotide, e.g., siRNA, described herein is capable of specifically binding to a region within a non-human primate IDO1 targeting nucleic acid sequence. An example of such a target nucleic acid sequence is the non-human primate IDO1 mRNA sequence set forth in SEQ ID NO: 13. Accordingly, in some aspects, siRNAs described herein comprise a contiguous nucleotide sequence that is capable of specifically binding to a region within the non-human primate IDO1 mRNA sequence set forth in SEQ ID NO: 13. More specifically, in some aspects, provided herein is an oligonucleotide, e.g., siRNA, comprising a continugous nucleotide sequence of about 10 to about 30 (e.g., about 14 to about 22) nucleotides in length, wherein the contiguous nucleotide sequence is complementary to a region within SEQ ID NO: 13. In some aspects, the target region corresponds to nucleotides 312-330 of SEQ ID NO: 13 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 312-330 of SEQ ID NO: 13 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the region corresponds to nucleotides 312-330 of SEQ ID NO: 13. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 312-330 of SEQ ID NO: 13 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 312-330 of SEQ ID NO: 13 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 312-330 of SEQ ID NO: 13. [0109] In some aspects, the target region corresponds to nucleotides 410-427 of SEQ ID NO: 13 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the target region corresponds to nucleotides 410-427 of SEQ ID NO: 13 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, the region corresponds to nucleotides 410-427 of SEQ ID NO: 13. Accordingly, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 410-427 of SEQ ID NO: 13 ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a nucleotide sequence of about 14 to about 22 nucleotides in length, wherein the contiguous nucleotide sequence is complementary to nucleotides 410-427 of SEQ ID NO: 13 ± 1, ± 2, ± 3, ± 4, ± 5, ± 6, ± 7, ± 8, ± 9, or ± 10 nucleotides at the 3' end, the 5' end, or both. In some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary to a region corresponding to nucleotides 410-427 of SEQ ID NO: 13. [0110] As further described elsewhere in the present disclosure, in some aspects, provided herein is an oligonucleotide, e.g., siRNA, comprising a contiguous nucleotide sequence that is capable of specifically binding to both a region within a human IDO1 target nucleic acid sequence and a region within a mouse IDO1 target nucleic acid sequence. For instance, in some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence of about 10 to about 30 (e.g., about 14 to about 22) nucleotides in length, wherein the contiguous nucleotide sequence is complementary to a region within SEQ ID NO: 1 (human IDO1 mRNA), to a region within SEQ ID NO: 3 (mouse IDO1 mRNA) and to a region within SEQ ID NO: 5 (mouse IDO1 mRNA). In some aspects, (i) the target region within SEQ ID NO: 1 corresponds to nucleotides 811-829 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both; (ii) the target region within SEQ ID NO: 3 corresponds to nucleotides 804-822 of SEQ ID NO: 3 ± 10 nucleotides at the 3' end, the 5' end, or both; (iii) the target region within SEQ ID NO: 5 corresponds to nucleotides 957-975 of SEQ ID NO: 5 ± 10 nucleotides at the 3' end, the 5' end, or both. To further illustrate, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary: (i) to a region corresponding to nucleotides 811-829 of SEQ ID NO: 1, (ii) to a region corresponding to nucleotides 804- 822 of SEQ ID NO: 3, and (iii) to a region corresponding to nucleotides 957-975 of SEQ ID NO: 5. In some aspects, (i) the target region within SEQ ID NO: 1 corresponds to nucleotides 528-546 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both; (ii) the target region within SEQ ID NO: 3 corresponds to nucleotides 521-539 of SEQ ID NO: 3 ± 10 nucleotides at the 3' end, the 5' end, or both; (iii) the target region within SEQ ID NO: 5 corresponds to nucleotides 674-692 of SEQ ID NO: 5 ± 10 nucleotides at the 3' end, the 5' end, or both. To further illustrate, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary: (i) to a region corresponding to nucleotides 528-546 of SEQ ID NO: 1, (ii) to a region corresponding to nucleotides 521-539 of SEQ ID NO: 3, and (iii) to a region corresponding to nucleotides 674-692 of SEQ ID NO: 5. [0111] As further described elsewhere in the present disclosure, in some aspects, provided herein is an oligonucleotide, e.g., siRNA, comprising a contiguous nucleotide sequence that is capable of specifically binding to both a region within a human IDO1 target nucleic acid sequence and a region within a non-human primate IDO1 target nucleic acid sequence. For instance, in some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence of about 10 to about 30 (e.g., about 14 to about 22) nucleotides in length, wherein the contiguous nucleotide sequence is complementary to a region within SEQ ID NO: 1 (human IDO1 mRNA), and to a region within SEQ ID NO: 13 (non-human primate IDO1 mRNA). In some aspects, (i) the target region within SEQ ID NO: 1 corresponds to nucleotides 327-345 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both; (ii) the target region within SEQ ID NO: 13 corresponds to nucleotides 312-330 of SEQ ID NO: 13 ± 10 nucleotides at the 3' end, the 5' end, or both. To further illustrate, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary: (i) to a region corresponding to nucleotides 327-345 of SEQ ID NO: 1, (ii) to a region corresponding to nucleotides 399-415 of SEQ ID NO: 3, (iii) to a region corresponding to nucleotides 552- 568 of SEQ ID NO: 5, (iv) to a region corresponding to nucleotides 472-488 of SEQ ID NO:11, and (v) to a region corresponding to nucleotides 312-330 of SEQ ID NO: 13. [0112] As further described elsewhere in the present disclosure, in some aspects, provided herein is an oligonucleotide, e.g., siRNA, comprising a contiguous nucleotide sequence that is capable of specifically binding to a region within a human IDO1 target nucleic acid sequence, a region within a mouse IDO1 target nucleic acid sequence, a region within a rabbit IDO1 mRNA, non-human primate IDO1 mRNA. For instance, in some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence of about 10 to about 30 (e.g., about 14 to about 22) nucleotides in length, wherein the contiguous nucleotide sequence is complementary to a region within SEQ ID NO: 1 (human IDO1 mRNA), to a region within SEQ ID NO: 3 (mouse IDO1 mRNA), to a region within SEQ ID NO: 5 (mouse IDO1 mRNA), to a region within SEQ ID NO: 7 (rabbit IDO1 mRNA), to a region within SEQ ID NO: 9 (rabbit IDO1 mRNA), and to a region within SEQ ID NO: 13 (non-human primate IDO1 mRNA). In some aspects, (i) the target region within SEQ ID NO: 1 corresponds to nucleotides 425-442 of SEQ ID NO: 1 ± 10 nucleotides at the 3' end, the 5' end, or both; (ii) the target region within SEQ ID NO: 3 corresponds to nucleotides 418-435 of SEQ ID NO: 3 ± 10 nucleotides at the 3' end, the 5' end, or both; (iii) the target region within SEQ ID NO: 5 corresponds to nucleotides 571- 588 of SEQ ID NO: 5 ± 10 nucleotides at the 3' end, the 5' end, or both; (iv) the target region within SEQ ID NO: 7 corresponds to nucleotides 463-480 of SEQ ID NO: 7 ± 10 nucleotides at the 3' end, the 5' end, or both; (v) the target region within SEQ ID NO: 9 corresponds to nucleotides 570-587 of SEQ ID NO: 9 ± 10 nucleotides at the 3' end, the 5' end, or both; (vi) the target region within SEQ ID NO: 13 corresponds to nucleotides 410- 427 of SEQ ID NO: 13 ± 10 nucleotides at the 3' end, the 5' end, or both. To further illustrate, in some aspects, an oligonucleotide, e.g., siRNA, provided herein comprises a contiguous nucleotide sequence of about 14 to about 22 nucleotides in length, wherien the contiguous nucleotide sequence is complementary: (i) to a region corresponding to nucleotides 425-442 of SEQ ID NO: 1, (ii) to a region corresponding to nucleotides 418- 435 of SEQ ID NO: 3, (iii) to a region corresponding to nucleotides 571-588 of SEQ ID NO: 5, (iv) to a region corresponding to nucleotides 463-480 of SEQ ID NO: 7, (v) to a region corresponding to nucleotides 570-587 of SEQ ID NO: 9, and (vi) to a region corresponding to nucleotides 410-427 of SEQ ID NO: 13. [0113] Accordingly, as is apparent from at least the above disclosure, in some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which is capable of binding to multiple (e.g., at least about two) IDO1 transcripts. More specifically, in some aspects, an oligonucleotide, e.g., siRNA, according to the present disclosure comprises a contiguous nucleotide sequence of about 10 to about 30 (e.g., about 14 to about 22) nucleotides in length, wherein the contiguous nucleotide sequence is complementary to a region within one or more of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, and SEQ ID NO: 13. [0114] In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence, which is capable of specifically binding to (i) a target region within the IDO1 transcript set forth in SEQ ID NO: 1, (ii) a target region within the IDO1 transcript set forth in SEQ ID NO: 3, and (iii) a target region within the IDO1 transcript set forth in SEQ ID NO: 5. In some aspects, two or more of: the target region within SEQ ID NO: 1, the target region within SEQ ID NO: 3, and the target region within SEQ ID NO: 5 are the same (i.e., comprises the same nucleic acid sequence). In some aspects, each of: the target region within SEQ ID NO: 1, the target region within SEQ ID NO: 3, and the target region within SEQ ID NO: 5 are not the same (i.e., comprises one or more nucleotide differences). [0115] In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence, which is capable of specifically binding to (i) a target region within the IDO1 transcript set forth in SEQ ID NO: 1, (ii) a target region within the IDO1 transcript set forth in SEQ ID NO: 3, (iii) a target region within the IDO1 transcript set forth in SEQ ID NO: 5, (iv) a target region within the IDO1 transcript set forth in SEQ ID NO: 11, and (v) a target region within the IDO1 transcript set forth in SEQ ID NO: 13. In some aspects, two or more of: the target region within SEQ ID NO: 1, the target region within SEQ ID NO: 3, the target region within SEQ ID NO: 5, the target region within SEQ ID NO: 11, and the target region within SEQ ID NO: 13 are the same (i.e., comprises the same nucleic acid sequence). In some aspects, each of: the target region within SEQ ID NO: 1, the target region within SEQ ID NO: 3, the target region within SEQ ID NO: 5, the target region within SEQ ID NO: 11, and the target region within SEQ ID NO: 13 are not the same (i.e., comprises one or more nucleotide differences). [0116] In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence, which is capable of specifically binding to (i) a target region within the IDO1 transcript set forth in SEQ ID NO: 1, (ii) a target region within the IDO1 transcript set forth in SEQ ID NO: 3, (iii) a target region within the IDO1 transcript set forth in SEQ ID NO: 5, (iv) a target region within the IDO1 transcript set forth in SEQ ID NO: 7, (v) a target region within the IDO1 transcript set forth in SEQ ID O: 9, and (vi) a target region within the IDO1 transcript set forth in SEQ ID NO: 13. In some aspects, two or more of: the target region within SEQ ID NO: 1, the target region within SEQ ID NO: 3, the target region within SEQ ID NO: 5, the target region within SEQ ID NO: 7, the target region within SEQ ID NO: 9, and the target region within SEQ ID NO: 13 are the same (i.e., comprises the same nucleic acid sequence). In some aspects, each of: the target region within SEQ ID NO: 1, the target region within SEQ ID NO: 3, the target region within SEQ ID NO: 5, the target region within SEQ ID NO: 7, the target region within SEQ ID NO: 9, and the target region within SEQ ID NO: 13 are not the same (i.e., comprises one or more nucleotide differences). [0117] In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which is not capable of specifically binding to one or more of the IDO1 transcripts provided herein. Accordingly, in some aspects, siRNAs described herein do not specifically bind to each of the IDO1 transcripts provided herein (e.g., IDO1 mRNAs set forth in SEQ NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, and SEQ ID NO: 13). In some aspects, an oligonucleotide, e.g., siRNA, useful for the present disclosure comprises a contiguous nucleotide sequence which is capable of only binding to two target regions, wherein the two target regions are selected from those within SEQ NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, and SEQ ID NO: 13. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which is capable of only binding to three target regions, wherein the three target regions are selected from those within SEQ NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, and SEQ ID NO: 13. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which is capable of only binding to four target regions, wherein the four target regions are selected from those within SEQ NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, and SEQ ID NO: 13. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which is capable of only binding to five target regions, wherein the five target regions are selected from those within SEQ NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, and SEQ ID NO: 13. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which is capable of only binding to six target regions, wherein the six target regions are selected from those within SEQ NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, and SEQ ID NO: 13. [0118] In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which does not specifically bind to a target region within SEQ ID NO: 11. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which does not specifically bind to a target region within SEQ ID NO: 13. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which does not specifically bind to both a target region within SEQ ID NO: 11 and a target region within SEQ ID NO: 13. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which does not specifically bind to both a target region within SEQ ID NO: 3 and a target region within SEQ ID NO: 13. [0119] In some aspects, the siRNA of the disclosure is capable of hybridizing to the target nucleic acid (e.g., IDO1 transcript) under physiological condition, i.e., in vivo condition. In some aspects, the siRNA of the disclosure is capable of hybridizing to the target nucleic acid (e.g., IDO1 transcript) in vitro. In some aspects, the siRNA of the disclosure is capable of hybridizing to the target nucleic acid (e.g., IDO1 transcript) in vitro under stringent conditions. Stringency conditions for hybridization in vitro are dependent on, inter alia, productive cell uptake, RNA accessibility, temperature, free energy of association, salt concentration, and time (see, e.g., Stanley T Crooks, Antisense Drug Technology: Principles, Strategies and Applications, 2^nd Edition, CRC Press (2007)). Generally, conditions of high to moderate stringency are used for in vitro hybridization to enable hybridization between substantially similar nucleic acids, but not between dissimilar nucleic acids. An example of stringent hybridization conditions include hybridization in 5X saline-sodium citrate (SSC) buffer (0.75 M sodium chloride/0.075 M sodium citrate) for 1 hour at 40° C, followed by washing the sample 10 times in 1X SSC at 40° C and 5 times in 1X SSC buffer at room temperature. In vivo hybridization conditions consist of intracellular conditions (e.g., physiological pH and intracellular ionic conditions) that govern the hybridization of small interfering RNAs with target sequences. In vivo conditions can be mimicked in vitro by relatively low stringency conditions. For example, hybridization can be carried out in vitro in 2X SSC (0.3 M sodium chloride/0.03 M sodium citrate), 0.1% SDS at 37°C. A wash solution containing 4X SSC, 0.1% SDS can be used at 37° C, with a final wash in 1X SSC at 45° C. II.B. siRNA Sequences [0120] The oligonucleotides, e.g., siRNAs, of the disclosure comprise a contiguous nucleotide sequence which corresponds to the complement of a region of an IDO1 transcript. As described herein, non-limiting examples of IDO1 transcript comprises a human IDO1 mRNA (e.g., SEQ ID NO: 1), mouse IDO1 mRNA (e.g., SEQ ID NO: 3 and 5), rabbit IDO1 mRNA (e.g., SEQ ID NO: 7 and 9), dog IDO1 mRNA (e.g., SEQ ID NO: 11), or non-human primate IDO1 mRNA (e.g., SEQ ID NO: 13). [0121] In some aspects, the disclosure provides an oligonucleotide, e.g., siRNA, which comprises a contiguous nucleotide sequence of about 10 to about 30 nucleotides (e.g., about 14 to about 22 nucleotides) in length, wherein the contiguous nucleotide sequence has at least about 85%, at least about 90%, at least about 95%, at least about 98%, or at least about 99% sequence identity to the complement of a region within an IDO1 transcript, such as that set forth in SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11 or SEQ ID NO: 13. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence, which has 100% sequence identity to the complement of a region within an IDO1 transcript. [0122] In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence, which has at least about 80% sequence identity to a sequence selected from SEQ ID NOs: 15-18 (i.e., the sequences in FIG.1), such as at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% sequence identity (homologous). [0123] In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence, which has at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the sequence set forth in SEQ ID NO: 15. In some aspects, an siRNA comprises the sequence set forth in SEQ ID NO: 15. In some aspects, an oligonucleotide, e.g., siRNA, consists of the sequence set forth in SEQ ID NO: 15. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of the sequence set forth in SEQ ID NO: 15. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence, which has at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the sequence set forth in SEQ ID NO: 16. In some aspects, an oligonucleotide, e.g., siRNA, comprises the sequence set forth in SEQ ID NO: 16. In some aspects, an oligonucleotide, e.g., siRNA, consists of the sequence set forth in SEQ ID NO: 16. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of the sequence set forth in SEQ ID NO: 16. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence, which has at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the sequence set forth in SEQ ID NO: 17. In some aspects, an oligonucleotide, e.g., siRNA, comprises the sequence set forth in SEQ ID NO: 17. In some aspects, an siRNA consists of the sequence set forth in SEQ ID NO: 17. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of the sequence set forth in SEQ ID NO: 17. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence, which has at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the sequence set forth in SEQ ID NO: 18. In some aspects, an oligonucleotide, e.g., siRNA, comprises the sequence set forth in SEQ ID NO: 18. In some aspects, an oligonucleotide, e.g., siRNA, consists of the sequence set forth in SEQ ID NO: 18. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of the sequence set forth in SEQ ID NO: 18. [0124] As described herein, in some aspects, siRNAs described herein comprise a contiguous nucleotide sequence which is fully complementary to a target region within an IDO1 transcript. However, as is apparent from the present disclosure, perfect (i.e., 100%) complementarity is not necessary for an oligonucleotide, e.g., siRNA, described herein to specifically target and bind (or hybridize) to a target region within an IDO1 transcript. In some aspects, the siRNAs described herein can tolerate about 1, about 2, about 3, or about 4 (or more) mismatches, when hybridizing to the target sequence and still sufficiently bind to the target to show the desired effect, i.e., down-regulation of the target mRNA and/or protein. Mismatches can, for example, be compensated by increased length of the oligonucleotide, e.g., siRNA, nucleotide sequence and/or an increased number of nucleotide analogs, which are disclosed elsewhere herein. [0125] In some aspects, the oligonucleotide, e.g., siRNA, of the disclosure comprises no more than about 3 mismatches when hybridizing to the target sequence (e.g., any of the sequences set forth in SEQ ID NOs: 1-14). In some aspects, the contiguous nucleotide sequence comprises no more than about 2 mismatches when hybridizing to the target sequence. In some aspects, the contiguous nucleotide sequence comprises no more than about 1 mismatch when hybridizing to the target sequence. [0126] It is recognized that, in some aspects, the nucleotide sequence of the oligonucleotide, e.g., siRNA, can comprise additional 5' or 3' nucleotides, such as, independently, 1, 2, 3, 4 or 5 additional nucleotides 5' and/or 3', which are non- complementary to the target sequence. In this respect the oligonucleotide, e.g., siRNA, of the disclosure, can, in some aspects, comprise a contiguous nucleotide sequence which is flanked 5' and/or 3' by additional nucleotides. In some aspects the additional 5' and/or 3' nucleotides are naturally occurring nucleotides, such as DNA or RNA. II.C. siRNA Length [0127] In some aspects, oligonucleotides, e.g., siRNAs, described herein generally comprise, consist of, or consist essentially of a contiguous nucleotide sequence which is about 10 to about 30 nucleotides length. For instance, in some aspects, the oligonucleotides, e.g., siRNAs, can comprise a contiguous nucleotide sequence of 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length. In some aspects, the oligonucleotides, e.g., siRNAs, consist of a contiguous nucleotide sequence of 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length. In some aspects, the oligonucleotides, e.g., siRNAs, described herein consist essentially of a contiguous nucleotide sequence of 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length. [0128] In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which is about 10 to about 20 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which is about 20 to about 30 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which is about 14 to about 22 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence which is about 14 to about 25 nucleotides in length. More specifically, in some aspects, an oligonucleotide, e.g., siRNA, comprises a contiguous nucleotide sequence which is about 14 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, comprises a contiguous nucleotide sequence which is about 15 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, comprises a contiguous nucleotide sequence which is about 16 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, comprises a contiguous nucleotide sequence which is about 17 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, comprises a contiguous nucleotide sequence which is about 18 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, comprises a contiguous nucleotide sequence which is about 19 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, comprises a contiguous nucleotide sequence which is about 20 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, comprises a contiguous nucleotide sequence which is about 21 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, comprises a contiguous nucleotide sequence which is about 22 nucleotides in length. [0129] In some aspects, an oligonucleotide, e.g., siRNA, described herein consists of a contiguous nucleotide sequence which is about 10 to about 20 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, described herein consists of a contiguous nucleotide sequence which is about 20 to about 30 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, described herein consists of a contiguous nucleotide sequence which is about 14 to about 22 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 14 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 15 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 16 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 17 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 18 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 19 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 20 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 21 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 22 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 23 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 24 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 25 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists of a contiguous nucleotide sequence which is about 26 nucleotides in length. [0130] In some aspects, an oligonucleotide, e.g., siRNA, described herein consists essentially of a contiguous nucleotide sequence which is about 10 to about 20 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, described herein consists essentially of a contiguous nucleotide sequence which is about 20 to about 30 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, described herein consists essentially of a contiguous nucleotide sequence which is about 14 to about 22 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 14 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 15 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 16 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 17 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 18 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 19 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 20 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 21 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 22 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 23 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 24 nucleotides in length. In some aspects, an oligonucleotide, e.g., siRNA, consists essentially of a contiguous nucleotide sequence which is about 25 nucleotides in length. II.D. Nucleosides and Nucleoside analogs [0131] In one aspect of the disclosure, the siRNAs comprise one or more non-naturally occurring nucleotide analogs. For instance, in some aspects, an oligonucleotide, e.g., siRNA, described herein comprises a contiguous nucleotide sequence of about 10 to about 30 (e.g., about 14 to about 22) nucleotides in length, wherein the contiguous nucleotide sequence is capable of specifically binding to a target region within an IDO1 transcript, and wherein the contiguous nucleotide sequence comprises one or more non-naturally occurring nucleotide analogs. [0132] "Nucleotide analogs" as used herein are variants of natural nucleotides, such as DNA or RNA nucleotides, by virtue of modifications in the sugar and/or base moieties. Analogs could in principle be merely "silent" or "equivalent" to the natural nucleotides in the context of the oligonucleotide, i.e. have no functional effect on the way the oligonucleotide works to inhibit target gene expression. Such "equivalent" analogs can nevertheless be useful if, for example, they are easier or cheaper to manufacture, or are more stable to storage or manufacturing conditions, or represent a tag or label. In some aspects, however, the analogs will have a functional effect on the way in which the oligonucleotide, e.g., siRNA, works to inhibit expression; for example by producing increased binding affinity to the target and/or increased resistance to intracellular nucleases and/or increased ease of transport into the cell. Specific examples of nucleoside analogs are described by e.g. Freier & Altmann; Nucl. Acid Res., 1997, 25, 4429-4443 and Uhlmann; Curr. Opinion in Drug Development, 2000, 3(2), 293-213, and in Scheme 1. II.D.1. Nucleobase [0133] The term nucleobase includes the purine (e.g., adenine and guanine) and pyrimidine (e.g., uracil, thymine and cytosine) moiety present in nucleosides and nucleotides which form hydrogen bonds in nucleic acid hybridization. In the context of the present disclosure the term nucleobase also encompasses modified nucleobases which can differ from naturally occurring nucleobases, but are functional during nucleic acid hybridization. In some aspects the nucleobase moiety is modified by modifying or replacing the nucleobase. In this context "nucleobase" refers to both naturally occurring nucleobases such as adenine, guanine, cytosine, thymidine, uracil, xanthine and hypoxanthine, as well as non-naturally occurring variants. Such variants are for example described in Hirao et al., (2012) Accounts of Chemical Research vol 45 page 2055 and Bergstrom (2009) Current Protocols in Nucleic Acid Chemistry Suppl.371.4.1. [0134] In a some aspects the nucleobase moiety is modified by changing the purine or pyrimidine into a modified purine or pyrimidine, such as substituted purine or substituted pyrimidine, such as a nucleobase selected from isocytosine, pseudoisocytosine, 5-methyl cytosine, 5-thiozolo-cytosine, 5-propynyl-cytosine, 5-propynyl-uracil, 5-bromouracil 5- thiazolo-uracil, 2-thio-uracil, 2’thio-thymine, inosine, diaminopurine, 6-aminopurine, 2- aminopurine, 2,6-diaminopurine and 2-chloro-6-aminopurine. [0135] The nucleobase moieties can be indicated by the letter code for each corresponding nucleobase, e.g., A, T, G, C or U, wherein each letter can optionally include modified nucleobases of equivalent function. For example, in the exemplified oligonucleotides, the nucleobase moieties are selected from A, T, G, C, and 5-methyl cytosine. Optionally, for LNA gapmers, 5-methyl cytosine LNA nucleosides can be used. II.D.2. Sugar Modification [0136] The oligonucleotide, e.g., siRNA, of the disclosure can comprise one or more nucleosides which have a modified sugar moiety, i.e. a modification of the sugar moiety when compared to the ribose sugar moiety found in DNA and RNA. Numerous nucleosides with modification of the ribose sugar moiety have been made, primarily with the aim of improving certain properties of oligonucleotides, such as affinity and/or nuclease resistance. [0137] Such modifications include those where the ribose ring structure is modified, e.g. by replacement with a hexose ring (HNA), or a bicyclic ring, which typically have a biradical bridge between the C2' and C4' carbons on the ribose ring (LNA), or an unlinked ribose ring which typically lacks a bond between the C2' and C3' carbons (e.g., UNA). Other sugar modified nucleosides include, for example, bicyclohexose nucleic acids (WO2011/017521) or tricyclic nucleic acids (WO2013/154798). Modified nucleosides also include nucleosides where the sugar moiety is replaced with a non-sugar moiety, for example in the case of peptide nucleic acids (PNA), or morpholino nucleic acids. [0138] Sugar modifications also include modifications made via altering the substituent groups on the ribose ring to groups other than hydrogen, or the 2’-OH group naturally found in RNA nucleosides. Substituents can, for example be introduced at the 2’, 3’, 4’ or 5’ positions. Nucleosides with modified sugar moieties also include 2’ modified nucleosides, such as 2’ substituted nucleosides. Indeed, much focus has been spent on developing 2’ substituted nucleosides, and numerous 2’ substituted nucleosides have been found to have beneficial properties when incorporated into oligonucleotides, such as enhanced nucleoside resistance and enhanced affinity. [0139] In some aspects, the sugar modification comprises an affinity enhancing sugar modification, e.g., LNA. An affinity enhancing sugar modification increases the binding affinity of the oligonucleotides, e.g., siRNAs, to the target RNA sequence (e.g., IDO1 mRNA). In some aspects, an oligonucleotide, e.g., siRNA, comprising a sugar modification disclosed herein has a binding affinity to a target RNA sequence that is enhanced by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100% compared to a control (e.g., an oligonucleotide, e.g., siRNA, without such sugar modification). II.D.2.a 2’ modified nucleosides [0140] A 2’ sugar modified nucleoside is a nucleoside which has a substituent other than H or –OH at the 2’ position (2’ substituted nucleoside) or comprises a 2’ linked biradical, and includes 2’ substituted nucleosides and LNA (2’ – 4’ biradical bridged) nucleosides. For example, the 2’ modified sugar can provide enhanced binding affinity and/or increased nuclease resistance to the oligonucleotide. Examples of 2’ substituted modified nucleosides are 2’-O-alkyl-RNA, 2’-O-methyl-RNA, 2’-alkoxy-RNA, 2’-O-methoxyethyl-RNA (MOE), 2’-amino-DNA, 2’-Fluoro-RNA, and 2’-F-ANA nucleoside. For further examples, please see e.g. Freier & Altmann; Nucl. Acid Res., 1997, 25, 4429-4443 and Uhlmann; Curr. Opinion in Drug Development, 2000, 3(2), 293-213, and Deleavey and Damha, Chemistry and Biology 2012, 19, 937. Below are illustrations of some 2’ substituted modified nucleosides.

II.D.2.b Locked Nucleic Acid Nucleosides (LNA). [0141] LNA nucleosides are modified nucleosides which comprise a linker group (referred to as a biradical or a bridge) between C2’ and C4’ of the ribose sugar ring of a nucleotide. These nucleosides are also termed bridged nucleic acid or bicyclic nucleic acid (BNA) in the literature. [0142] In some aspects, the modified nucleoside or the LNA nucleosides of the siRNA of the disclosure has a general structure of the formula II or III:

Formula II Formula III wherein W is selected from -O-, -S-, -N(R^a)-, -C(R^aR^b)-, such as, in some aspects –O-; B designates a nucleobase or modified nucleobase moiety; Z designates an internucleoside linkage to an adjacent nucleoside, or a 5'-terminal group; Z* designates an internucleoside linkage to an adjacent nucleoside, or a 3'-terminal group; and X designates a group selected from the group consisting of -C(R^aR^b)-, -C(R^a)=C(R^b)-, -C(R^a)=N-, -O-, -Si(R^a)₂-, -S-, - SO2-, -N(R^a)-, and >C=Z. [0143] In some aspects, X is selected from the group consisting of: –O-, -S-, NH-, NR^aR^b, -CH₂-, CR^aR^b, -C(=CH₂)-, and -C(=CR^aR^b)-. In some aspects, X is -O-. [0144] In some aspects, Y designates a group selected from the group consisting of - C(R^aR^b)-, -C(R^a)=C(R^b)-, -C(R^a)=N-, -O-, -Si(R^a)2-, -S-, -SO2-, -N(R^a)-, and >C=Z. In some aspects, Y is selected from the group consisting of: –CH2-, -C(R^aR^b)-, –CH2CH2-, - C(R^aR^b)-C(R^aR^b)-, –CH₂CH₂CH₂-, -C(R^aR^b)C(R^aR^b)C(R^aR^b)-, -C(R^a)=C(R^b)-, and - C(R^a)=N-. [0145] In some aspects, Y is selected from the group consisting of: -CH₂-, -CHR^a-, - CHCH3-, CR^aR^b-, and -X-Y- together designate a bivalent linker group (also referred to as a radicle) together designate a bivalent linker group consisting of 1, 2, 3 or 4 groups/atoms selected from the group consisting of -C(R^aR^b)-, -C(R^a)=C(R^b)-, -C(R^a)=N-, -O-, -Si(R^a)₂- , -S-, -SO2-, -N(R^a)-, and >C=Z. [0146] In some aspects, -X-Y designates a biradical selected from the groups consisting of: -X-CH₂-, -X-CR^aR^b-, -X-CHR^a-, -X-C(HCH₃)-, -O-Y-, -O-CH₂-, -S-CH₂-, -NH-CH₂-, -O- CHCH₃-, -CH₂-O-CH₂, -O-CH(CH₃CH₃)-, -O-CH₂-CH₂-, OCH₂-CH₂-CH₂-,-O-CH₂OCH₂- , -O-NCH2-, -C(=CH2)-CH2-, -NR^a-CH2-, N-O-CH2, -S-CR^aR^b- and -S-CHR^a-. [0147] In some aspects –X-Y- designates –O-CH₂- or –O-CH(CH₃)-. [0148] In some aspects, Z is selected from -O-, -S-, and -N(R^a)-, and R^a and, when present R^b, each is independently selected from hydrogen, optionally substituted C1-6-alkyl, optionally substituted C2-6-alkenyl, optionally substituted C2-6-alkynyl, hydroxy, optionally substituted C_1-6-alkoxy, C_2-6-alkoxyalkyl, C_2-6-alkenyloxy, carboxy, C_1-6-alkoxycarbonyl, C1-6-alkylcarbonyl, formyl, aryl, aryloxy-carbonyl, aryloxy, arylcarbonyl, heteroaryl, heteroaryloxy-carbonyl, heteroaryloxy, heteroarylcarbonyl, amino, mono- and di(C1-6- alkyl)amino, carbamoyl, mono- and di(C_1-6-alkyl)-amino-carbonyl, amino-C_1-6-alkyl- aminocarbonyl, mono- and di(C_1-6-alkyl)amino-C_1-6-alkyl-aminocarbonyl, C_1-6-alkyl- carbonylamino, carbamido, C1-6-alkanoyloxy, sulphono, C1-6-alkylsulphonyloxy, nitro, azido, sulphanyl, C_1-6-alkylthio, halogen, where aryl and heteroaryl can be optionally substituted and where two geminal substituents R^a and R^b together can designate optionally substituted methylene (=CH2), wherein for all chiral centers, asymmetric groups can be found in either R or S orientation. [0149] In some aspects, R¹, R², R³, R⁵ and R^5* are independently selected from the group consisting of: hydrogen, optionally substituted C1-6-alkyl, optionally substituted C2-6- alkenyl, optionally substituted C2-6-alkynyl, hydroxy, C1-6-alkoxy, C2-6-alkoxyalkyl, C2-6- alkenyloxy, carboxy, C_1-6-alkoxycarbonyl, C_1-6-alkylcarbonyl, formyl, aryl, aryloxy- carbonyl, aryloxy, arylcarbonyl, heteroaryl, heteroaryloxy-carbonyl, heteroaryloxy, heteroarylcarbonyl, amino, mono- and di(C1-6-alkyl)amino, carbamoyl, mono- and di(C1-6- alkyl)-amino-carbonyl, amino-C_1-6-alkyl-aminocarbonyl, mono- and di(C_1-6-alkyl)amino- C_1-6-alkyl-aminocarbonyl, C_1-6-alkyl-carbonylamino, carbamido, C_1-6-alkanoyloxy, sulphono, C1-6-alkylsulphonyloxy, nitro, azido, sulphanyl, C1-6-alkylthio, and halogen, where aryl and heteroaryl can be optionally substituted, and where two geminal substituents together can designate oxo, thioxo, imino, or optionally substituted methylene. [0150] In some aspects R¹, R², R³, R⁵ and R^5* are independently selected from C1-6 alkyl, such as methyl, and hydrogen. [0151] In some aspects R¹, R², R³, R⁵ and R^5* are all hydrogen. [0152] In some aspects R¹, R², R³, are all hydrogen, and either R⁵ and R^5* is also hydrogen and the other of R⁵ and R^5*is other than hydrogen, such as C_1-6 alkyl such as methyl. [0153] In some aspects, R^a is either hydrogen or methyl. In some aspects, when present, R^b is either hydrogen or methyl. [0154] In some aspects, one or both of R^a and R^b is hydrogen. [0155] In some aspects, one of R^a and R^b is hydrogen and the other is other than hydrogen. [0156] In some aspects, one of R^a and R^b is methyl and the other is hydrogen. [0157] In some aspects, both of R^a and R^b are methyl. [0158] In some aspects, the biradical –X-Y- is –O-CH₂-, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such LNA nucleosides are disclosed in WO99/014226, WO00/66604, WO98/039352 and WO2004/046160 which are all hereby incorporated by reference, and include what are commonly known as beta-D-oxy LNA and alpha-L-oxy LNA nucleosides. [0159] In some aspects, the biradical –X-Y- is –S-CH2-, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such thio LNA nucleosides are disclosed in WO99/014226 and WO2004/046160. [0160] In some aspects, the biradical –X-Y- is –NH-CH2-, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such amino LNA nucleosides are disclosed in WO99/014226 and WO2004/046160. [0161] In some aspects, the biradical –X-Y- is –O-CH2-CH2- or –O-CH2-CH2- CH2-, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such LNA nucleosides are disclosed in WO00/047599 and Morita et al., Bioorganic & Med.Chem. Lett. 1273-76, which are hereby incorporated by reference, and include what are commonly known as 2’-O-4’C- ethylene bridged nucleic acids (ENA). [0162] In some aspects, the biradical –X-Y- is –O-CH₂-, W is O, and all of R¹, R², R³, and one of R⁵ and R^5* are hydrogen, and the other of R⁵ and R^5* is other than hydrogen such as C1-6 alkyl, such as methyl. Such 5’ substituted LNA nucleosides are disclosed in WO2007/134181. [0163] In some aspects, the biradical –X-Y- is –O-CR^aR^b-, wherein one or both of R^a and R^b are other than hydrogen, such as methyl, W is O, and all of R¹, R², R³, and one of R⁵ and R^5* are hydrogen, and the other of R⁵ and R^5* is other than hydrogen such as C1-6 alkyl, such as methyl. Such bis modified LNA nucleosides are disclosed in WO2010/077578. [0164] In some aspects, the biradical –X-Y- designate the bivalent linker group –O- CH(CH2OCH3)- (2’ O-methoxyethyl bicyclic nucleic acid - Seth at al., 2010, J. Org. Chem. Vol 75(5) pp.1569-81). In some aspects, the biradical –X-Y- designate the bivalent linker group –O-CH(CH₂CH₃)- (2’O-ethyl bicyclic nucleic acid - Seth at al., 2010, J. Org. Chem. Vol 75(5) pp.1569-81). In some aspects, the biradical –X-Y- is –O-CHR^a-, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such 6’ substituted LNA nucleosides are disclosed in WO10036698 and WO07090071. [0165] In some aspects, the biradical –X-Y- is –O-CH(CH2OCH3)-, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such LNA nucleosides are also known as cyclic MOEs in the art (cMOE) and are disclosed in WO07090071. [0166] In some aspects, the biradical –X-Y- designates the bivalent linker group –O- CH(CH3)-. – in either the R- or S- configuration. In some aspects, the biradical –X-Y- together designate the bivalent linker group –O-CH₂-O-CH₂- (Seth et al., 2010, J. Org. Chem). In some aspects, the biradical –X-Y- is –O-CH(CH₃)-, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such 6’ methyl LNA nucleosides are also known as cET nucleosides in the art, and can be either (S)cET or (R)cET stereoisomers, as disclosed in WO07090071 (beta-D) and WO2010/036698 (alpha-L)). [0167] In some aspects, the biradical –X-Y- is –O-CR^aR^b-, wherein in neither R^a or R^b is hydrogen, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. In some aspects, R^a and R^b are both methyl. Such 6’ di-substituted LNA nucleosides are disclosed in WO 2009006478. [0168] In some aspects, the biradical –X-Y- is –S-CHR^a-, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such 6’ substituted thio LNA nucleosides are disclosed in WO11156202. In some 6’ substituted thio LNA aspects R^a is methyl. [0169] In some aspects, the biradical –X-Y- is –C(=CH2)-C(R^aR^b)-, such as –C(=CH2)- CH₂- , or –C(=CH₂)-CH(CH₃)-W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such vinyl carbo LNA nucleosides are disclosed in WO08154401 and WO09067647. [0170] In some aspects the biradical –X-Y- is –N(-OR^a)-, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. In some aspects R^a is C_1-6 alkyl such as methyl. Such LNA nucleosides are also known as N substituted LNAs and are disclosed in WO2008/150729. In some aspects, the biradical –X-Y- together designate the bivalent linker group –O-NR^a- CH3- (Seth et al., 2010, J. Org. Chem). In some aspects the biradical –X-Y- is –N(R^a)-, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. In some aspects R^a is C_1-6 alkyl such as methyl. [0171] In some aspects, one or both of R⁵ and R^5* is hydrogen and, when substituted the other of R⁵ and R^5* is C_1-6 alkyl such as methyl. In such an aspect, R¹, R², R³, can all be hydrogen, and the biradical –X-Y- can be selected from –O-CH2- or –O-CH(CR^a)-, such as –O-CH(CH3)-. [0172] In some aspects, the biradical is –CR^aR^b-O-CR^aR^b-, such as CH₂-O-CH₂-, W is O and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. In some aspects R^a is C_1-6 alkyl such as methyl. Such LNA nucleosides are also known as conformationally restricted nucleotides (CRNs) and are disclosed in WO2013036868. [0173] In some aspects, the biradical is –O-CR^aR^b-O-CR^aR^b-, such as O-CH₂-O-CH₂-, W is O and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. In some aspects R^a is C1-6 alkyl such as methyl. Such LNA nucleosides are also known as COC nucleotides and are disclosed in Mitsuoka et al., Nucleic Acids Research 200937(4), 1225-1238. [0174] It will be recognized than, unless specified, the LNA nucleosides can be in the beta- D or alpha-L stereoisoform. [0175] Certain examples of LNA nucleosides are presented in Scheme 1.

Scheme 1

[0176] As illustrated in the examples, in some aspects of the disclosure the LNA nucleosides in the oligonucleotides are beta-D-oxy-LNA nucleosides. II.E. Nuclease mediated degradation [0177] In some aspects, the oligonucleotides, e.g., siRNA, described herein can interact with and activate a RNA-induced silencing complex (RISC). The endonuclease argonaute 2 (AGO2) component of the RISC can cleave the passenger strand (sense strand) of the siRNA while the guide strand (antisense strand) remains associated with the RISC. Subsequently, the guide strand can guide the active RISC to its target mRNA for cleavage by AGO2. As the guide strand only binds to mRNA that is fully complementary to it, siRNA can cause specific gene silencing. [0178] dsRNA (either transcribed or artificially introduced) can be processed by Dicer into siRNA which is loaded into the RISC. AGO2, which is a component of the RISC, cleaves the passenger strand of the siRNA. The guide strand then can guide the active RISC to the target mRNA. The full complementary binding between the guide strand of the siRNA and the target mRNA can lead to the cleavage of the mRNA. II.G. siRNA Design [0179] The oligonucleotide, e.g., siRNA, of the disclosure can comprise a nucleotide sequence which comprises both nucleotides and nucleotide analogs, and can be in the form of a gapmer. Examples of configurations of a gapmer that can be used with the oligonucleotide, e.g., siRNA, of the disclosure are described in U.S. Patent Appl. Publ. No. 2012/0322851. [0180] The term gapmer as used herein refers to a small interfering RNA which comprises a region of nucleotides (e.g., an oligonucleotide) (gap) which is flanked 5’ and 3’ by one or more affinity enhancing modified nucleosides (flanks). Various gapmer designs are described herein. The term LNA gapmer is a gapmer oligonucleotide wherein at least one of the affinity enhancing modified nucleosides is an LNA nucleoside. The term mixed wing gapmer refers to a LNA gapmer wherein the flank regions comprise at least one LNA nucleoside and at least one DNA nucleoside or non-LNA modified nucleoside, such as at least one 2’ substituted modified nucleoside, such as, for example, 2'-O-alkyl-RNA, 2'-O- methyl-RNA, 2'-alkoxy-RNA, 2'-O-methoxyethyl-RNA (MOE), 2'-amino-DNA, 2'- Fluoro-RNA and 2'-F-ANA nucleoside(s). In some aspects the mixed wing gapmer has one flank which comprises LNA nucleosides (e.g., 5' or 3') and the other flank (3' or 5' respectfully) comprises 2' substituted modified nucleoside(s). II.H. Internucleotide Linkages [0181] The monomers of the oligonucleotide, e.g., siRNA, described herein are coupled together via linkage groups. Suitably, each monomer is linked to the 3' adjacent monomer via a linkage group. [0182] The person having ordinary skill in the art would understand that, in the context of the present disclosure, the 5' monomer at the end of an siRNA does not comprise a 5' linkage group, although it can or cannot comprise a 5' terminal group. [0183] The terms "linkage group" and "internucleotide linkage" are intended to mean a group capable of covalently coupling together two nucleotides. Specific and preferred examples include phosphate groups and phosphorothioate groups. [0184] The nucleotides of the oligonucleotide, e.g., siRNA, of the disclosure or contiguous nucleotides sequence thereof are coupled together via linkage groups. Suitably each nucleotide is linked to the 3' adjacent nucleotide via a linkage group. [0185] Suitable internucleotide linkages include those listed within WO2007/031091, for example the internucleotide linkages listed on the first paragraph of page 34 of WO2007/031091 (hereby incorporated by reference in its entirety). [0186] Examples of suitable internucleotide linkages that can be used with the disclosure include phosphodiester linkage, a phosphotriester linkage, a methylphosphonate linkage, a phosphoramidate linkage, a phosphorothioate linkage, and combinations thereof. [0187] It is, in some aspects, preferred to modify the internucleotide linkage from its normal phosphodiester to one that is more resistant to nuclease attack, such as phosphorothioate or boranophosphate, as to allow cleavage of the targeted RNA and thus reduce expression of the targeted gene. [0188] Suitable sulphur (S) containing internucleotide linkages as provided herein can be preferred. Phosphorothioate internucleotide linkages are also preferred, particularly for the gap region (B) of gapmers. Phosphorothioate linkages can also be used for the flanking regions (A and C, and for linking A or C to D, and within region D, as appropriate). [0189] Regions A, B and C, can, however, comprise internucleotide linkages other than phosphorothioate, such as phosphodiester linkages, particularly, for instance when the use of nucleotide analogs protects the internucleotide linkages within regions A and C from endo-nuclease degradation – such as when regions A and C comprise LNA nucleotides. [0190] The internucleotide linkages in the oligonucleotide, e.g., siRNA, can be phosphodiester, phosphorothioate or boranophosphate so as to allow cleavage of the targeted RNA. Phosphorothioate is preferred for improved nuclease resistance and other reasons, such as ease of manufacture. In some aspects, the internucleotide linkages comprise one or more stereo-defined internucleotide linkages (e.g., such as stereo-defined modified phosphate linkages, e.g., phosphodiester, phosphorothioate, or boranophosphate linkages with a defined stereochemical structure). The term "stereo-defined internucleotide linkage" is used interchangeably with "chirally controlled internucleotide linkage" and refers to a internucleotide linkage in which the stereochemical designation of the phosphorus atom is controlled such that a specific amount of R_p or S_p of the internucleotide linkage is present within an oligonucleotide, e.g., siRNA, strand. The stereochemical designation of a chiral linkage can be defined (controlled) by, for example, asymmetric synthesis. An oligonucleotide, e.g., siRNA, having at least one stereo-defined internucleotide linkage can be called as a stereo-defined oligonucleotide, e.g., siRNA, which includes both a fully stereo-defined oligonucleotide, e.g., siRNA, and a partially stereo-defined oligonucleotide, e.g., siRNA. [0191] In some aspects, an oligonucleotide, e.g., siRNA, is fully stereo-defined. A fully stereo-defined oligonucleotide, e.g., siRNA, refers to an oligonucleotide, e.g., siRNA, sequence having a defined chiral center (R_p or S_p) in each internucleotide linkage in the oligonucleotide, e.g., siRNA. In some aspects, an oligonucleotide, e.g., siRNA, is partially stereo-defined. A partially stereo-defined oligonucleotide, e.g., siRNA, refers to an oligonucleotide, e.g., siRNA, sequence having a defined chiral center (Rp or Sp) in at least one internucleotide linkage, but not in all of the internucleotide linkages. Therefore, a partially stereo-defined oligonucleotide, e.g., siRNA, can include linkages that are achiral or stereo-nondefined in addition to the at least one stereo-defined linkage. When an internucleotide linkage in an oligonucleotide, e.g., siRNA, is stereo-defined, the desired configuration, either R_p or S_p, is present in at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or essentially 100% of the oligonucleotide, e.g., siRNA. [0192] In one aspect of the oligonucleotide, e.g., siRNA, of the disclosure, the nucleotides and/or nucleotide analogs are linked to each other by means of phosphorothioate groups. [0193] It is recognized that the inclusion of phosphodiester linkages, such as one or two linkages, into an otherwise phosphorothioate oligonucleotide, e.g., siRNA, particularly between or adjacent to nucleotide analog units (typically in region A and or C) can modify the bioavailability and/or bio-distribution of an oligonucleotide, e.g., siRNA– see WO2008/113832, hereby incorporated by reference. [0194] In some aspects, such as the aspects referred to above, where suitable and not specifically indicated, all remaining linkage groups are either phosphodiester or phosphorothioate, or a mixture thereof. [0195] In some aspects all the internucleotide linkage groups are phosphorothioate. [0196] When referring to specific gapmer oligonucleotide sequences, such as those provided herein it will be understood that, in various aspects, when the linkages are phosphorothioate linkages, alternative linkages, such as those disclosed herein can be used, for example phosphate (phosphodiester) linkages can be used, particularly for linkages between nucleotide analogs, such as LNA, units. Likewise, when referring to specific gapmer oligonucleotide sequences, such as those provided herein, when the C residues are annotated as 5-'methyl modified cytosine, in various aspects, one or more of the Cs present in the oligonucleotide, e.g., siRNA, can be unmodified C residues. [0197] In some aspects, an oligonucleotide, e.g., siRNA, compounds described herein can have at least one bicyclic nucleoside attached to the 3' or 5' termini by a neutral internucleoside linkage. The oligonucleotides, e.g., siRNAs, of the disclosure can therefore have at least one bicyclic nucleoside attached to the 3' or 5' termini by a neutral internucleoside linkage, such as one or more phosphotriester, methylphosphonate, MMI (3′-CH₂—N(CH₃)—O-5′), amide-3 (3′-CH₂—C(═O)—N(H)-5′), formacetal (3′-O— CH2—O-5′) or thioformacetal (3′-S—CH2—O-5′). The remaining linkages can be phosphorothioate. II.I. Conjugates [0198] The term conjugate as used herein refers to an oligonucleotide, e.g., siRNA, which is covalently linked to a non-nucleotide moiety (conjugate moiety or region C or third region). [0199] Conjugation of the oligonucleotide, e.g., siRNA, of the disclosure to one or more non-nucleotide moieties can improve the pharmacology of the oligonucleotide, e.g., siRNA, e.g. by affecting the activity, cellular distribution, cellular uptake or stability of the oligonucleotide. In some aspects the conjugate moiety modify or enhance the pharmacokinetic properties of the oligonucleotide by improving cellular distribution, bioavailability, metabolism, excretion, permeability, and/or cellular uptake of the oligonucleotide, e.g., siRNA. In particular the conjugate can target the oligonucleotide, e.g., siRNA, to a specific organ, tissue or cell type and thereby enhance the effectiveness of the oligonucleotide, e.g., siRNA, in that organ, tissue or cell type. At the same time the conjugate can serve to reduce activity of the oligonucleotide, e.g., siRNA, in non-target cell types, tissues or organs, e.g., off target activity or activity in non-target cell types, tissues or organs. WO 93/07883 and WO2013/033230 provides suitable conjugate moieties. Further suitable conjugate moieties are those capable of binding to the asialoglycoprotein receptor (ASGPr). In particular tri-valent N-acetylgalactosamine conjugate moieties are suitable for binding to the ASGPr, see for example WO 2014/076196, WO 2014/207232 and WO 2014/179620. [0200] Oligonucleotide, e.g., siRNA, conjugates and their synthesis has also been reported in comprehensive reviews by Manoharan in Antisense Drug Technology, Principles, Strategies, and Applications, S.T. Crooke, ed., Ch. 16, Marcel Dekker, Inc., 2001 and Manoharan, Antisense and Nucleic Acid Drug Development, 2002, 12, 103. [0201] In an aspect, the non-nucleotide moiety (conjugate moiety) is selected from the group consisting of carbohydrates, cell surface receptor ligands, drug substances, hormones, lipophilic substances, polymers, proteins, peptides, toxins (e.g. bacterial toxins), vitamins, viral proteins (e.g. capsids), and combinations thereof. II.J. Activated siRNAs [0202] The term "activated siRNA," as used herein, refers to an oligonucleotide, e.g., siRNA, of the disclosure that is covalently linked (i.e., functionalized) to at least one functional moiety that permits covalent linkage of the oligonucleotide, e.g., siRNA, to one or more conjugated moieties, i.e., moieties that are not themselves nucleic acids or monomers, to form the conjugates herein described. Typically, a functional moiety will comprise a chemical group that is capable of covalently bonding to the oligonucleotide, e.g., siRNA, via, e.g., a 3'-hydroxyl group or the exocyclic NH₂ group of the adenine base, a spacer that can be hydrophilic and a terminal group that is capable of binding to a conjugated moiety (e.g., an amino, sulfhydryl or hydroxyl group). In some aspects, this terminal group is not protected, e.g., is an NH₂ group. In some aspects, the terminal group is protected, for example, by any suitable protecting group such as those described in "Protective Groups in Organic Synthesis" by Theodora W Greene and Peter G M Wuts, 3rd edition (John Wiley & Sons, 1999). [0203] In some aspects, oligonucleotides, e.g., siRNAs, of the disclosure are functionalized at the 5' end in order to allow covalent attachment of the conjugated moiety to the 5' end of the oligonucleotide, e.g., siRNA,. In some aspects, oligonucleotides, e.g., siRNAs, of the disclosure can be functionalized at the 3' end. In still some aspects, oligonucleotides, e.g., siRNAs, of the disclosure can be functionalized along the backbone or on the heterocyclic base moiety. In yet some aspects, oligonucleotides, e.g., siRNAs, of the disclosure can be functionalized at more than one position independently selected from the 5' end, the 3' end, the backbone and the base. [0204] In some aspects, activated oligonucleotides, e.g., siRNAs, of the disclosure are synthesized by incorporating during the synthesis one or more monomers that is covalently attached to a functional moiety. In some aspects, activated oligonucleotides, e.g., siRNAs, of the disclosure are synthesized with monomers that have not been functionalized, and the oligonucleotide, e.g., siRNA, is functionalized upon completion of synthesis. III. Pharmaceutical Compositions and Administration Routes [0205] The oligonucleotide, e.g., siRNA, of the disclosure can be used in pharmaceutical formulations and compositions. Suitably, such compositions comprise a pharmaceutically acceptable diluent, carrier, salt or adjuvant. [0206] The oligonucleotide, e.g., siRNA, of the disclosure can be included in a unit formulation such as in a pharmaceutically acceptable carrier or diluent in an amount sufficient to deliver to a patient a therapeutically effective amount without causing serious side effects in the treated patient. However, in some forms of therapy, serious side effects can be acceptable in terms of ensuring a positive outcome to the therapeutic treatment. [0207] The formulated drug can comprise pharmaceutically acceptable binding agents and adjuvants. Capsules, tablets, or pills can contain for example the following compounds: microcrystalline cellulose, gum or gelatin as binders; starch or lactose as excipients; stearates as lubricants; various sweetening or flavoring agents. For capsules the dosage unit can contain a liquid carrier like fatty oils. Likewise coatings of sugar or enteric agents can be part of the dosage unit. The oligonucleotide formulations can also be emulsions of the active pharmaceutical ingredients and a lipid forming a micellular emulsion. [0208] The pharmaceutical compositions of the present disclosure can be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration can be (a) oral (b) pulmonary, e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, (c) topical including epidermal, transdermal, ophthalmic and to mucous membranes including vaginal and rectal delivery; or (d) parenteral including intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial, e.g., intrathecal, intra-cerebroventricular, or intraventricular, administration. In one aspect the oligonucleotide, e.g., siRNA, is administered IV, IP, orally, topically or as a bolus injection or administered directly in to the target organ. In one aspect, the oligonucleotide, e.g., siRNA, is administered intrathecal or intra-cerebroventricular as a bolus injection. [0209] Pharmaceutical compositions and formulations for topical administration can include transdermal patches, ointments, lotions, creams, gels, drops, sprays, suppositories, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like can be necessary or desirable. Examples of topical formulations include those in which the oligonucleotide, e.g., siRNA, of the disclosure are in admixture with a topical delivery agent such as lipids, liposomes, fatty acids, fatty acid esters, steroids, chelating agents and surfactants. Compositions and formulations for oral administration include but are not limited to powders or granules, microparticulates, nanoparticulates, suspensions or solutions in water or non-aqueous media, capsules, gel capsules, sachets, tablets or minitablets. Compositions and formulations for parenteral, intrathecal, intra- cerebroventricular, or intraventricular administration can include sterile aqueous solutions which can also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carrier compounds and other pharmaceutically acceptable carriers or excipients. [0210] Pharmaceutical compositions of the present disclosure include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions can be generated from a variety of components that include, but are not limited to, preformed liquids, self-emulsifying solids and self-emulsifying semisolids. Delivery of drug to the target tissue can be enhanced by carrier-mediated delivery including, but not limited to, cationic liposomes, cyclodextrins, porphyrin derivatives, branched chain dendrimers, polyethylenimine polymers, nanoparticles and microspheres (Dass CR. J Pharm Pharmacol 2002; 54(1):3-27). [0211] The pharmaceutical formulations of the present disclosure, which can conveniently be presented in unit dosage form, can be prepared according to conventional techniques well known in the pharmaceutical industry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product. [0212] For parenteral, subcutaneous, intradermal or topical administration the formulation can include a sterile diluent, buffers, regulators of tonicity and antibacterials. The active oligonucleotides, e.g., siRNAs, can be prepared with carriers that protect against degradation or immediate elimination from the body, including implants or microcapsules with controlled release properties. For intravenous administration the carriers can be physiological saline or phosphate buffered saline. International Publication No. WO2007/031091 (A2), published March 22, 2007, further provides suitable pharmaceutically acceptable diluent, carrier and adjuvants - which are hereby incorporated by reference. IV. Kits comprising siRNAs [0213] This disclosure further provides kits that comprise an oligonucleotide, e.g., siRNA, of the disclosure described herein and that can be used to perform the methods described herein. In some aspects, a kit comprises at least one oligonucleotide, e.g., siRNA, in one or more containers. In some aspects, the kits contain all of the components necessary and/or sufficient to perform a detection assay, including all controls, directions for performing assays, and any necessary software for analysis and presentation of results. One skilled in the art will readily recognize that the disclosed oligonucleotide, e.g., siRNA, can be readily incorporated into one of the established kit formats which are well known in the art. V. Methods of Using [0214] The oligonucleotides, e.g., siRNAs, of the disclosure can be utilized in various therapeutic settings. Non-limiting examples of such therapeutic uses are described below. V.A. IDO1 Protein Expression [0215] As is apparent from the present disclosure, oligonucleotides, e.g., siRNAs, of the present disclosure are particularly useful in reducing/inhibiting the expression of an IDO1 protein in a cell. For instance, as described herein, oligonucleotides, e.g., siRNAs, of the present disclosure are capable of specifically binding to a region within an IDO1 transcript, wherein the binding reduces/inhibits the expression of an IDO1 protein in the cell. Accordingly, some aspects of the present disclosure relates to a method of inhibiting or reducing IDO1 protein expression in a cell comprising an IDO1 transcript, the method comprising contacting the cell with any of the oligonucleotides, e.g., siRNAs, provided herein. As it will be apparent to those skilled in the arts, the expression "contacting the cell with any of the oligonucleotides, e.g., siRNAs, provided herein" (or derivatives thereof) comprises contacting the cells with the oligonucleotides, e.g., siRNAs, themselves but can also comprise contacting the cells with any other compositions comprising the oligonucleotides, e.g., siRNAs, (e.g., conjugates or pharmaceutical compositions). In some aspects, after the contacting, the IDO1 protein expression is inhibited or reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference cell (e.g., corresponding cell that is not contacted and/or the cell prior to the contacting). [0216] Not to be bound by any one theory, in some aspects, the binding of an oligonucleotide, e.g., siRNA, to a target region within an IDO1 transcript, reduces the level of the IDO1 transcript in the cell and thereby, resulting in decreased expression of the encoded IDO1 protein in the cell. As a result, some aspects of the present disclosure is related to method of inhibiting or reducing IDO1 transcript level in a cell comprising the IDO1 transcript, the method comprising contacting the cell with any of the oligonucleotides, e.g., siRNAs, described herein. In some aspects, after the contacting, the IDO1 transcript level is inhibited or reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference cell (e.g., corresponding cell that is not contacted and/or the cell prior to the contacting). [0217] In any of the above methods, the oligonucleotides, e.g., siRNAs, described herein can be contacted with the cells using any suitable methods known in the art, such that the oligonucleotides, e.g., siRNAs, are intracellularly delivered to the cells and bind to a target region within an IDO1 transcript. Non-limiting examples of such methods include transfection electroporation, nanoparticle delivery, viral vector delivery and others. In some aspects, the contacting between an oligonucleotide, e.g., siRNA, and a cell occurs ex vivo (e.g., in vitro). In some aspects, the contacting occurs in vivo. For instance, where the contacting occurs in vivo, an oligonucleotide, e.g., siRNA, described herein can be administered to the subject prior to the contacting. V.B. Tryptophan Conversion [0218] Tryptophan is an essential amino acid that cannot be synthesized by animals and must be supplied in the diet. The tryptophan catabolism pathway plays an important role in tumor cell evasion of the innate and adaptive immune systems. Tryptophan is generally utilized in three major metabolic pathways: incorporation into proteins, production of serotonin, and breakdown into kynurenine. The kynurenine pathway is responsible for the production of nicotinamide dinucleotide (NAD) and also has immunoregulatory effects. [0219] There are three rate-limiting enzymes that catalyze the conversion tryptophan to N- formyl kynurenine, indoleamine 2, 3-dioxygenase 1 (IDO1), indoleamine 2, 3-dioxygenase 2 (IDO2) and tryptophan 2, 3-dioxygenase (TDO). IDO1 and IDO2 are responsible for the generation of kynurenine in peripheral tissues, while TDO is active in the hepatic system. IDO1 is expressed in many cell types including fibroblasts, mesenchymal stromal cells, and immune cells, such as monocytes, macrophages and dendritic cells. In these cells, expression of IDO1 is induced by inflammatory cytokines, in particular IFN-γ. [0220] IDO1 is the most well characterized and has immunoregulatory functions. In healthy individuals, IDO1 facilitates tolerance by reducing the immune response. During gestation, IDO1 helps protect the fetus from maternal T lymphocytes. [0221] In inflammatory and tumor microenvironments, IDO1 regulates the immune response by depleting tryptophan. IDO1 is overexpressed in tumor cells of the vast majority of cancers. In the tumor microenvironment, IDO1 depletes tryptophan by converting it to kynurenine. Together, depletion of tryptophan and production of kynurenine reduce the antitumor response and promote neovascularization in the tumor microenvironment. T cells, a major component of the antitumor response, sense depletion of tryptophan by the kinase general control nonderepressible 2 (GCN2) which inhibits T cell proliferation upon activation. Tryptophan depletion also inhibits the mammalian target of rapamycin (mTOR), which triggers autophagy, leading to anergy in T cells in the tumor microenvironment. mTOR inhibition in CD4⁺ T cells also induces T regulatory cell (T_reg) differentiation. Additionally, kynurenine is an endogenous ligand of the aryl hydrocarbon receptor (AhR) which promotes naïve CD4⁺ T cell differentiation into Treg cells. Therefore, IDO1 depletion of tryptophan via the production of kynurenine contributes to an immunosuppressive tumor microenvironment. [0222] Accordingly, some aspects of the present disclosure is directed to methods of reducing the conversion of tryptophan to kynurenine in a cell of a subject in need thereof, comprising administering to the subject any of the oligonucleotides, e.g., siRNAs, described herein. As it will be apparent to those skilled in the arts, the expression "administering to the subject any of the oligonucleotides, e.g., siRNAs, provided herein" (or derivatives thereof) comprises administering to the subject the oligonucleotides, e.g., siRNAs, themselves but can also comprise administering any other compositions comprising the oligonucleotides, e.g., siRNAs, (e.g., conjugates or pharmaceutical compositions). In some aspects, after the administration, the conversion of tryptophan to kynurenine in the cell is reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). [0223] Not to be bound by any one theory, in some aspects, by reducing/inhibiting the conversion of tryptophan (e.g., to kynurenine), the tryptophan level in the subject (e.g., within a cell or blood) can be increased as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). In some aspects, by reducing tryptophan conversion, it is possible to stabilize tryptophan levels within the subject (e.g., with a cell or blood of the subject). Accordingly, some aspects of the present disclosure is related to a method of increasing or stabilizing tryptophan level in a subject in need thereof, comprising administering to the subject any of the siRNAs described herein. In some aspects, after the administration, the tryptophan level in a cell of the subject is increased by at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, at least about 10-fold, at least about 15-fold, at least about 20-fold, at least about 25-fold, at least about 30-fold, at least about 35-fold, at least about 40-fold, or at least about 50-fold, as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). In some aspects, after the administration, the tryptophan level in a blood of the subject is increased by at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, at least about 10-fold, at least about 15-fold, at least about 20-fold, at least about 25-fold, at least about 30-fold, at least about 35-fold, at least about 40-fold, or at least about 50-fold, as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). [0224] As is apparent from at least the above disclosure, in some aspects, the present disclosure relates to a method of reducing kynurenine level in a subject in need thereof, comprising administering to the subject any of the oligonucleotides, e.g., siRNAs, described herein. In some aspects, after the administration, the kynurenine level in a cell of the subject is reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). In some aspects, after the administration, the kynurenine level in a blood of the subject is reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). V.C. Cancer Treatment [0225] As described above, the tryptophan and/or kynurenine level within a subject is closely related to the immunosuppressive nature of a tumor microenvironment. Accordingly, in some aspects, by increasing the tryptophan level and/or decreasing the kynurenine level (e.g., by reducing the conversion of tryptophan to kynurenine) within a subject, the immunosuppressive nature of a tumor microenvironment can be reduced/inhibited. And, in some aspects, the reduced immunosuppressive nature of the tumor microenvironment can allow for greater anti-cancer effects. [0226] In some aspects, provided herein is a method of reducing the immunosuppressive nature of a tumor microenvironment in a subject in need thereof, comprising administering to the subject any of the oligonucleotides, e.g., siRNAs, described herein. In some aspects, after the administration, the immunosuppressive nature of a tumor microenvironment is reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference cell (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). [0227] Some aspects of the present disclosure relates to a method of treating a cancer in a subject in need thereof, comprising administering to the subject any of the oligonucleotides, e.g., siRNAs, described herein. The particular cancers that can be treated with the present disclosure are not particularly limited, as long as reducing the level of an IDO1 protein can exert a therapeutic effect on the cancer. Non-limiting examples of cancers that can be treated with the present disclosure includes: a glioblastoma, glioblastoma multiforme, colorectal cancer, hepatocytoma, hepatoma, squamous cell carcinoma, small-cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), squamous NSCLC, nonsquamous NSCLC, glioma, gastrointestinal cancer, renal cancer, clear cell carcinoma, ovarian cancer, liver cancer, endometrial cancer, kidney cancer, renal cell carcinoma (RCC), prostate cancer, hormone refractory prostate adenocarcinoma, thyroid cancer, neuroblastoma, pancreatic cancer, cervical cancer, stomach cancer, bladder cancer, breast cancer, colon carcinoma, head and neck cancer, gastric cancer, germ cell tumor, pediatric sarcoma, sinonasal natural killer, melanoma, bone cancer, skin cancer, uterine cancer, cancer of the anal region, testicular cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, rectal cancer, solid tumors of childhood, cancer of the ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain cancer, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid cancer, squamous cell cancer, environmentally-induced cancers including those induced by asbestos, virus-related cancers or cancers of viral origin (e.g., human papilloma virus (HPV-related or -originating tumors)), an IDO1 expressing cancer, or any combinations thereof. [0228] In some aspects, the oligonucleotides, e.g., siRNAs, described herein (or any other compositions described herein comprising the oligonucleotides, e.g., siRNAs,, e.g., pharmaceutical composition) can be administered to the subject alone. In some aspects, the oligonucleotides, e.g., siRNAs, (or any other compositions described herein comprising the oligonucleotides, e.g., siRNAs, e.g., pharmaceutical composition) can be administered to the subject in combination with one or more additional therapeutic agents. In some aspects, the one or more additional therapeutic agents allow for the targeting of multiple elements of the immune pathway. Non-limiting of such combinations include: a therapy that enhances tumor antigen presentation (e.g., dendritic cell vaccine, GM-CSF secreting cellular vaccines, CpG oligonucleotides, imiquimod); a therapy that inhibits negative immune regulation e.g., by inhibiting CTLA-4 and/or PD1/PD-L1/PD-L2 pathway and/or depleting or blocking T_regs or other immune suppressing cells (e.g., myeloid-derived suppressor cells); a therapy that stimulates positive immune regulation, e.g., with agonists that stimulate the CD-137, OX-40, and/or CD40 or GITR pathway and/or stimulate T cell effector function; a therapy that increases systemically the frequency of anti-tumor T cells; a therapy that depletes or inhibits T_regs, such as T_regs in the tumor, e.g., using an antagonist of CD25 (e.g., daclizumab) or by ex vivo anti-CD25 bead depletion; a therapy that impacts the function of suppressor myeloid cells in the tumor; a therapy that enhances immunogenicity of tumor cells (e.g., anthracyclines); adoptive T cell or NK cell transfer including genetically modified cells, e.g., cells modified by chimeric antigen receptors (CAR-T therapy); a therapy that inhibits a metabolic enzyme such as indoleamine dioxygenase (IDO), dioxygenase, arginase, or nitric oxide synthetase; a therapy that reverses/prevents T cell anergy or exhaustion; a therapy that triggers an innate immune activation and/or inflammation at a tumor site; administration of immune stimulatory cytokines; blocking of immuno repressive cytokines; or any combination thereof. [0229] In some aspects, an additional therapeutic agent that can be used with the oligonucleotides, e.g., siRNAs, described herein comprise: a chemotherapeutic drug, targeted anti-cancer therapy, oncolytic drug, cytotoxic agent, immune-based therapy, cytokine, surgical procedure, radiation procedure, activator of a costimulatory molecule, immune checkpoint inhibitor, a vaccine, a cellular immunotherapy, or any combination thereof. [0230] In some aspects, an anti-cancer agent comprises an immune checkpoint inhibitor (i.e., blocks signaling through the particular immune checkpoint pathway). Non-limiting examples of immune checkpoint inhibitors that can be used in the present methods comprise a CTLA-4 antagonist, a LAG-3 antagonist, a TIM3 antagonist, a TIGIT antagonist, a TIM3 antagonist, a NKG2a antagonist, an OX40 antagonist, an ICOS antagonist, a MICA antagonist, a CD137 antagonist, a KIR antagonist, a TGFβ antagonist, an IL-10 antagonist, an IL-8 antagonist, a B7-H4 antagonist, a Fas ligand antagonist, a CXCR4 antagonist, a mesothelin antagonist, a CD27 antagonist, a GITR antagonist, a PD- 1 antagonist, a PD-L1 antagonist or any combination thereof. Non-limiting examples of such immune checkpoint inhibitors include the following: anti-PD1 antibody (e.g., nivolumab (OPDIVO^®), pembrolizumab (KEYTRUDA^®; MK-3475), pidilizumab (CT- 011), PDR001, MEDI0680 (AMP-514), TSR-042, REGN2810, JS001, AMP-224 (GSK- 2661380), PF-06801591, BGB-A317, BI 754091, SHR-1210, and combinations thereof); anti-PD-L1 antibody (e.g., atezolizumab (TECENTRIQ^®; RG7446; MPDL3280A; RO5541267), durvalumab (MEDI4736, IMFINZI^®), BMS-936559, avelumab (BAVENCIO^®), LY3300054, CX-072 (Proclaim-CX-072), FAZ053, KN035, MDX-1105, and combinations thereof); and anti-CTLA-4 antibody (e.g., ipilimumab (YERVOY^®), tremelimumab (ticilimumab; CP-675,206), AGEN-1884, ATOR-1015, and combinations thereof). In some aspects, the anti-cancer agent can comprise other anti-cancer agents known in the art, such as those described in Saluja R, et al., “Examining Trends in Cost and Clinical Benefit of Novel Anticancer Drugs Over Time.” J Oncol Pract. 2018 May;14(5):e280-e294, which is incorporated herein by reference in its entirety. [0231] In some aspects, an additional therapeutic agent that can be used in combination with oligonucleotides, e.g., siRNAs, described herein comprises an angiogenesis inhibitor. Non-limiting examples of such angiogenesis inhibitors include: a VEGF antagonist, a VEGFR antagonist, a FGF antagonist, a PDGF antagonist, a TGF antagonist, an angiopoietin antagonist, a HER2 antagonist, bevacizumab, axitinib, everolimus, cabozantinib, lenalidomide, lenvatinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, thalidomide, ziv-afibercept and vandetanib or any combination thereof. In some aspects, the angiogenesis inhibitor can comprise other angiogenesis inhibitors known in the art, such as those disclosed in Ayoub NM, et al. “Targeting Angiogenesis in Breast Cancer: Current Evidence and Future Perspectives of Novel Anti-Angiogenic Approaches.” Front Pharmacol.2022 Feb 25;13:838133 and Ansari MJ, et al. “Cancer combination therapies by angiogenesis inhibitors; a comprehensive review”. Cell Commun Signal. 2022 Apr 7;20(1):49., each of which are incorporated herein by reference in their entireties. [0232] In some aspects, an additional therapeutic agent that can be used with the oligonucleotides, e.g., siRNAs, described herein comprises an adoptive cell therapy. In some aspects, the adoptive cell therapy comprises T cells expressing a chimeric antigen receptor (CAR-T cells), NK cells expressing a chimeric antigen receptor (CAR-NK cells), any other immune cells expressing a chimeric antigen receptor, or any combination thereof. In some aspects, an additional therapeutic agent comprises a topoisomerase inhibitor, a DNA methyltransferase inhibitor, a DNA intercalator, ixabepilone, bendamustine hydrochloride, eribulin mesylate, cabazitaxel, emtansine, trabectedin, nanoliposomal irinotecan, TAS-102, etoposide, carboplatin, cisplatin, doxorubicin, temozolomide, or any combination thereof. [0233] In some aspects, an siRNA described herein (or any composition comprising the oligonucleotides, e.g., siRNAs,, e.g., pharmaceutical composition) is administered to the subject prior to or after the administration of the additional therapeutic agent. In some aspects, the oligonucleotide, e.g., siRNA, is administered to the subject concurrently with the additional therapeutic agent. In some aspects, the oligonucleotide, e.g., siRNA, and the additional therapeutic agent can be administered concurrently as a single composition in a pharmaceutically acceptable carrier. In some aspects, the oligonucleotide, e.g., siRNA, and the additional therapeutic agent are administered concurrently as separate compositions. V.D. Neuronal Disease Treatment [0234] As is apparent from the present disclosure, the oligonucleotides, e.g., siRNAs, described herein (which can specifically target and reduce the expression of an IDO1 protein) can be used to treat a neuronal disease which are associated with abnormal IDO1 activity and/or expression. Accordingly, in some aspects, provided herein is a method of treating a neuronal disease in a subject in need thereof, comprising administering to the subject any of the oligonucleotides, e.g., siRNAs, provided herein. Non-limiting examples of neuronal diseases that can be treated include: Alzheimer’s disease (AD), multiple system atrophy, Parkinson’s disease (PD), Parkinson's Disease Dementia (PDD), dementia with Lewy bodies, vascular and mixed dementia, Amytrophic Lateral Sclerosis (ALS) and any combinations thereof. [0235] In some aspects, an additional therapeutic agent that can be used with the oligonucleotides, e.g., siRNAs, described herein comprises an agent to treat a neuronal disease. In some aspects, the agent to treat a neuronal disease an acetylcholinesterase inhibitor, an NMDA antagonist, a dopamine supplement, a DOPA decarboxylase inhibitor, a Catechol-o-methyltransferase (COMT) inhibitor, a monoamine oxidase (MAO) inhibitor, an NMDA antagonist, an antioxidant, an antichorea drug, donepezil, rivastigmine, memantine, levodopa, carbidopa, benserazide, tolcapone, entacapone, selegiline, rasagiline, riluzole, edaravone, tetrabenazine or any combination thereof. In some aspects, the agent to treat a neuronal disease can comprise any other agent to treat a neuronal disease known in the art, such as those described in Muddapu VR, et al. “Neurodegenerative Diseases - Is Metabolic Deficiency the Root Cause?” Front Neurosci.2020 Mar 31;14:213., which is incorporated herein by reference in its entirety. [0236] In some aspects, an oligonucleotide, e.g., siRNA, described herein (or any composition comprising the oligonucleotides, e.g., siRNAs, e.g., pharmaceutical composition) is administered to the subject prior to or after the administration of the additional therapeutic agent. In some aspects, the oligonucleotide, e.g., siRNA, is administered to the subject concurrently with the additional therapeutic agent. In some aspects, the oligonucleotide, e.g., siRNA, and the additional therapeutic agent can be administered concurrently as a single composition in a pharmaceutically acceptable carrier. In some aspects, the oligonucleotide, e.g., siRNA, and the additional therapeutic agent are administered concurrently as separate compositions. [0237] The practice of the present disclosure will employ, unless otherwise indicated, conventional techniques of cell biology, cell culture, molecular biology, transgenic biology, microbiology, recombinant DNA, and immunology, which are within the skill of the art. Such techniques are explained fully in the literature. See, for example, Sambrook et al., ed. (1989) Molecular Cloning A Laboratory Manual (2nd ed.; Cold Spring Harbor Laboratory Press); Sambrook et al., ed. (1992) Molecular Cloning: A Laboratory Manual, (Cold Springs Harbor Laboratory, NY); D. N. Glover ed., (1985) DNA Cloning, Volumes I and II; Gait, ed. (1984) Oligonucleotide Synthesis; Mullis et al. U.S. Pat. No.4,683,195; Hames and Higgins, eds. (1984) Nucleic Acid Hybridization; Hames and Higgins, eds. (1984) Transcription And Translation; Freshney (1987) Culture Of Animal Cells (Alan R. Liss, Inc.); Immobilized Cells And Enzymes (IRL Press) (1986); Perbal (1984) A Practical Guide To Molecular Cloning; the treatise, Methods In Enzymology (Academic Press, Inc., N.Y.); Miller and Calos eds. (1987) Gene Transfer Vectors For Mammalian Cells, (Cold Spring Harbor Laboratory); Wu et al., eds., Methods In Enzymology, Vols.154 and 155; Mayer and Walker, eds. (1987) Immunochemical Methods In Cell And Molecular Biology (Academic Press, London); Weir and Blackwell, eds., (1986) Handbook Of Experimental Immunology, Volumes I-IV; Manipulating the Mouse Embryo, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., (1986); ); Crooke, Antisense drug Technology: Principles, Strategies and Applications, 2^nd Ed. CRC Press (2007) and in Ausubel et al. (1989) Current Protocols in Molecular Biology (John Wiley and Sons, Baltimore, Md.). [0238] All of the references cited above, as well as all references cited herein, are incorporated herein by reference in their entireties. [0239] The following examples are offered by way of illustration and not by way of limitation. EXAMPLES Example 1: Construction of siRNAs [0240] Small interfering RNAs described herein were designed to target various regions in both human and mouse IDO1 mRNA transcripts or in both human and non-human primate IDO1 mRNA transcripts. Human and mouse mRNA sequences were aligned, and regions with completely matched sequences of length 14-22 nucleotides were selected as targets. See FIG. 1 for IDO1 siRNA sequences. See FIG 2 and 3 for human (FIG. 2) and mouse (FIG. 3) IDO1 mRNA sequences with siRNA target sequences indicated by boxes. Similarly, to produce the siRNAs targeting both human and non-human primate IDO1 mRNA transcripts, human and non-human primate mRNA sequences were aligned, and regions with completely matched sequences of length 14-22 nucleotides were selected as targets. The siRNAs were synthesized using methods well known in the art. Example 2: Assay to Measure Reduction of IDO1 Protein in HeLa Cells [0241] siRNAs targeting IDO1 were tested for their ability to reduce IDO1 protein expression in HeLa cells. [0242] HeLa cells were plated at 3.5 x 10⁴ cells/well in 24-well plates and incubated overnight with complete DMEM medium. The wells were treated with 20 to 100 nM of siIDO1-1 to siIDO1-4 with 0.1 to 0.25 μL of RNAiMAX for 6 h. After replacement with fresh complete DMEM medium containing IFN- γ (5 ng/ml), the cells were incubated for additional 48 h. A mix of non-functional siRNAs was used as a negative control (NC). After 48 h, the cells were harvested for Western blot analysis. [0243] FIG. 4 shows the IDO1 protein level of HeLa cells after treatment with IDO1 siRNAs. As shown, as compared to the NC group, each of the IDO1-targeting siRNAs provided herein was able to reduce IDO1 protein expression to varying degrees. Example 3: Concentration of the siRNAs [0244] To assess the effect of siRNA concentration on the potency of the siRNAs provided herein, the expression of IDO1 protein in HeLa cells was measured after treatment with different low concentrations of IDO1 siRNAs. HeLa cells were cultured at 3.5 x 10⁴ cells/well in 24-well plates and incubated overnight with complete DMEM medium. The wells were treated with 10 to 20 nM of siIDO1-1 to siIDO1-4 with 0.1 μL of RNAiMAX for 6 h. After replacement with fresh complete DMEM medium containing IFN-γ (5 ng/ml), the cells were incubated for additional 48 h. No treatment (NT) was used as a negative control and indicates no treatment with IFN- γ. After 48 h, the cells were harvested for Western blot analysis. [0245] FIG 5 shows the IDO1 protein level of HeLa cells after treatment with the siRNAs is dose dependent. [0246] Collectively, the above results confirm the therapeutic capability of the siRNAs described herein.

Claims

WHAT IS CLAIMED 1. A small interfering RNA (siRNA) comprising a contiguous nucleotide sequence of 14 to 22 nucleotides in length that is complementary to a nucleic acid sequence within an indoleamine 2,3-dioxygenase 1 (IDO1) transcript, wherein the IDO1 transcript is selected from SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, or a combination thereof. 2. The small interfering RNA of claim 1, which is capable of binding to two or more of the IDO1 transcripts. 3. The small interfering RNA of claim 2, which is capable of binding to the IDO1 transcripts set forth in SEQ ID NOs: 1 and 3. 4. The small interfering RNA of claim 2, which is capable of binding to the IDO1 transcripts set forth in SEQ ID NOs: 1, 3, and 5. 5. The small interfering RNA of claim 2, which is capable of binding to the IDO1 transcripts set forth in SEQ ID NOs: 1, 3, 5, and 13. 6. The small interfering RNA of claim 2, which is capable of binding to the IDO1 transcripts set forth in SEQ ID NOs: 1, 3, 5, 7, 9, and 13. 7. The small interfering RNA of claim 2, which does not bind to: (i) the IDO1 transcript set forth in SEQ ID NO: 11, (ii) the IDO1 transcript set forth in SEQ ID NO: 13, or (iii) both (i) and (ii). 8. The small interfering RNA of claim 2, which does not bind to: (i) the IDO1 transcript set forth in SEQ ID NO: 7, (ii) the IDO1 transcript set forth in SEQ ID NO: 9, or (iii) both (i) and (ii). 9. The small interfering RNA of claim 2, which is capable of binding only to: (i) the IDO1 transcript set forth in SEQ ID NO: 1, (ii) the IDO1 transcript set forth in SEQ ID NO: 3, (iii) the IDO1 transcript set forth in SEQ ID NO: 5, or (iv) any combination of (i) to (iii). 10. The small interfering RNA of any one of claims 1 to 9, wherein the nucleic acid sequence comprises: (a) nucleotides 317-355 of SEQ ID NO: 1, (b) nucleotides 518-556 of SEQ ID NO: 1, (c) nucleotides 801-839 of SEQ ID NO: 1, (d) nucleotides 415-452 of SEQ ID NO: 1, (e) nucleotides 511-549 of SEQ ID NO: 3, (f) nucleotides 794-832 of SEQ ID NO: 3, (g) nucleotides 408-445 of SEQ ID NO: 3, (h) nucleotides 664-702 of SEQ ID NO: 5, (i) nucleotides 947-985 of SEQ ID NO: 5, (j) nucleotides 561-598 of SEQ ID NO: 5, (k) nucleotides 453-490 of SEQ ID NO: 7, (l) nucleotides 560-597 of SEQ ID NO: 9, (m) nucleotides 302-340 of SEQ ID NO: 13, (n) nucleotides 400-437 of SEQ ID NO: 13, or (o) a combination thereof. 11. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 811-829 of SEQ ID NO: 1. 12. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 327-345 of SEQ ID NO: 1. 13. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 425-442 of SEQ ID NO: 1. 14. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 528-546 of SEQ ID NO: 1. 15. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 804-822 of SEQ ID NO: 3. 16. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 418-435 of SEQ ID NO: 3. 17. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 521-539 of SEQ ID NO: 3. 18. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 957-975 of SEQ ID NO: 5. 19. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 571-588 of SEQ ID NO: 5. 20. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 674-692 of SEQ ID NO: 5. 21. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 463-480 of SEQ ID NO: 7. 22. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 570-587 of SEQ ID NO: 9. 23. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 312-330 of SEQ ID NO: 13. 24. The small interfering RNA of claim 10, wherein the nucleic acid sequence comprises nucleotides 410-427 of SEQ ID NO: 13. 25. The small interfering RNA of any one of claims 1 to 24, wherein the contiguous nucleotide sequence comprises SEQ ID NO: 15 to SEQ ID NO: 18 with one, two, or three mismatches. 26. The small interfering RNA of any one of claims 1 to 24, wherein the contiguous nucleotide sequence comprises SEQ ID NO: 15 to SEQ ID NO: 18. 27. The small interfering RNA of claim 1, wherein the contiguous nucleotide sequence comprises SEQ ID NO: 15. 28. The small interfering RNA of claim 1, wherein the contiguous nucleotide sequence comprises SEQ ID NO: 16. 29. The small interfering RNA of claim 1, wherein the contiguous nucleotide sequence comprises SEQ ID NO: 17. 30. The small interfering RNA of claim 1, wherein the contiguous nucleotide sequence comprises SEQ ID NO: 18. 31. The small interfering RNA of any one of claims 1 to 30, wherein the binding of the small interfering RNA to the IDO1 transcript is capable of inhibiting the expression of the IDO1 protein in a cell which comprises the IDO1 transcript. 32. The small interfering RNA of any one of claims 1 to 31, which is capable of reducing the conversion of tryptophan to kynurenine in a cell when contacted with the cell. 33. The small interfering RNA of any one of claims 1 to 32, which is capable of increasing or stabilizing tryptophan levels in a cell when contacted with the cell. 34. The small interfering RNA of any one of claims 1 to 33, wherein the small interfering RNA is capable of reducing or stabilizing kynurenine levels in a cell when contacted with the cell. 35. The small interfering RNA of any one of claims 31 to 34, wherein the cell comprises a neuronal cell, a tumor cell, an immune cell, an endothelial cell, a mesenchymal cell, a fibroblast cell, any other cell of the tumor micro-environment, or any combination thereof. 36. The small interfering RNA of any of claims 1 to 35, wherein the contiguous nucleotide sequence comprises at least one nucleotide analogue. 37. The small interfering RNA of claim 36, wherein the nucleotide analogue or analogues are one or more sugar modified nucleosides comprising Locked Nucleic Acid (LNA); 2'-O- alkyl-RNA; 2'-amino-DNA; 2'-fluoro-DNA; arabino nucleic acid (ANA); 2'-fluoro-ANA, hexitol nucleic acid (HNA), intercalating nucleic acid (INA), constrained ethyl nucleoside (cEt), 2'-O-methyl nucleic acid (2'-OMe), 2'-O-methoxyethyl nucleic acid (2'-MOE), and any combination thereof. 38. The small interfering RNA of any one of claims 36 or 37, wherein the nucleotide analogue or analogues comprise a bicyclic sugar. 39. The small interfering RNA of claim 38, wherein the bicyclic sugar comprises cEt, 2',4'- constrained 2′-O-methoxyethyl (cMOE), LNA, α-L-LNA, β-D-LNA, 2'-O,4'-C-ethylene- bridged nucleic acids (ENA), amino-LNA, oxy-LNA, or thio-LNA. 40. The small interfering RNA of any one of claims 36 or 37, wherein the nucleotide analogue or analogues comprise an LNA. 41. The small interfering RNA of any one of claims 36 or 37, wherein the small interfering RNA comprises one or more 5' methyl cytosine nucleobases. 42. The small interfering RNA of claim 40, which comprises two to five LNAs on the 5' region of the small interfering RNA. 43. The small interfering RNA of claim 40, which comprises two to five LNAs on the 3' region of the small interfering RNA. 44. The small interfering RNA of any one of claims 1 to 43, which has 14, 15, 16, 17, 18, 19, 20, 21, or 22 nucleotides in length. 45. The small interfering RNA of claim 44, which has 14 nucleotides in length. 46. The small interfering RNA of claim 44, which has 19 nucleotides in length. 47. The small interfering RNA of claim 44, which has 20 nucleotides in length. 48. The small interfering RNA of any one of claims 1 to 47, which comprises an internucleoside linkage selected from: a phosphodiester linkage, a phosphotriester linkage, a methylphosphonate linkage, a phosphoramidate linkage, a phosphorothioate linkage, and combinations thereof. 49. The small interfering RNA of claim 48, wherein the internucleoside linkage comprises one or more stereo-defined, modified phosphate linkages. 50. A small interfering RNA comprising, consisting essentially of, or consisting of the contiguous nucleotide sequence set forth in any one of SEQ ID NOs: 15 to 18. 51. A small interfering RNA comprising, consisting essentially of, or consisting of the contiguous nucleotide sequence set forth in SEQ ID NO: 15. 52. A small interfering RNA comprising, consisting essentially of, or consisting of the contiguous nucleotide sequence set forth in SEQ ID NO: 16. 53. A small interfering RNA comprising, consisting essentially of, or consisting of the contiguous nucleotide sequence set forth in SEQ ID NO: 17. 54. A small interfering RNA comprising, consisting essentially of, or consisting of the contiguous nucleotide sequence set forth in SEQ ID NO: 18. 55. A conjugate comprising the small interfering RNA of any one of claims 1 to 54, wherein the small interfering RNA is covalently attached to at least one non-nucleotide or non- polynucleotide moiety. 56. The conjugate of claim 55, wherein the non-nucleotide or non-polynucleotide moiety comprises a protein, a fatty acid chain, a sugar residue, a glycoprotein, a polymer, a steroid, or any combination thereof. 57. A pharmaceutical composition comprising the small interfering RNA of any one claims 1 to 54 or the conjugate of claim 55 or 56 and a pharmaceutically acceptable carrier. 58. A kit comprising the small interfering RNA of any one claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57, and instructions for use. 59. A method of inhibiting or reducing IDO1 protein expression in a cell comprising the IDO1 transcript, the method comprising contacting the cell with the small interfering RNA of any one claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57, wherein the IDO1 protein expression in the cell is inhibited or reduced after the contacting. 60. The method of claim 59, wherein the IDO1 protein expression is inhibited or reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference cell (e.g., corresponding cell that is not contacted and/or the cell prior to the contacting). 61. A method of inhibiting or reducing IDO1 transcript level in a cell comprising the IDO1 transcript, the method comprising contacting the cell with the small interfering RNA of any one claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57, wherein the IDO1 transcript level in the cell is inhibited or reduced after the contacting. 62. The method of claim 61, wherein the IDO1 transcript level is inhibited or reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference cell (e.g., corresponding cell that is not contacted and/or the cell prior to the contacting). 63. The method of any one of claims 59 to 62, wherein the cell comprises a tumor cell, an immune cell, an endothelial cell, a mesenchymal cell, a fibroblast cell, any other cell of the tumor micro-environment, or any combination thereof. 64. The method of any one of claims 59 to 63, wherein the contacting occurs ex vivo. 65. The method of any one of claims 59 to 63, wherein the contacting occurs in vivo. 66. The method of claim 65, which comprises administering the small interfering RNA, the conjugate, or the pharmaceutical composition to a subject in need thereof prior to the contacting. 67. A method of reducing the conversion of tryptophan to kynurenine in a cell of a subject in need thereof, comprising administering to the subject the small interfering RNA of any one claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57. 68. The method of claim 67, wherein the conversion of tryptophan to kynurenine in the cell is reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). 69. A method of increasing or stabilizing tryptophan level in a cell or in the blood of a subject in need thereof, comprising administering to the subject the small interfering RNA of any one claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57. 70. The method of claim 69, wherein the tryptophan level is increased by at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, at least about 10-fold, at least about 15-fold, at least about 20-fold, at least about 25-fold, at least about 30-fold, at least about 35-fold, at least about 40-fold, or at least about 50-fold, as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). 71. A method of reducing or stabilizing kynurenine level in a cell or in the blood of a subject in need thereof, comprising administering to the subject the small interfering RNA of any one claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57. 72. The method of claim 71, wherein the kynurenine level is reduced by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100%, as compared to that of a reference subject (e.g., corresponding subject that did not receive the administration and/or the subject prior to the administration). 73. A method of treating a cancer in a subject in need thereof, comprising administering to the subject the small interfering RNA of any one claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57. 74. The method of any one of claims 66 to 73, which further comprises administering an additional therapeutic agent to the subject. 75. The method of claim 74, wherein the additional therapeutic agent comprises an anticancer agent (chemotherapy), a radiation therapy, or a combination thereof. 76. The method of claim 75, wherein the anticancer agent comprises an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor comprises a CTLA-4 antagonist, a LAG-3 antagonist, a TIM3 antagonist, a TIGIT antagonist, a TIM3 antagonist, a NKG2a antagonist, an OX40 antagonist, an ICOS antagonist, a MICA antagonist, a CD137 antagonist, a KIR antagonist, a TGFβ antagonist, an IL-10 antagonist, an IL-8 antagonist, a B7-H4 antagonist, a Fas ligand antagonist, a CXCR4 antagonist, a mesothelin antagonist, a CD27 antagonist, a GITR antagonist, a PD-1 antagonist, a PD-L1 antagonist or any combination thereof. 77. The method of claim 75, wherein the anticancer agent comprises an angiogenesis inhibitor, wherein the angiogenesis inhibitor comprises a VEGF antagonist, a VEGFR antagonist, a FGF antagonist, a PDGF antagonist, a TGF antagonist, an angiopoietin antagonist, a HER2 antagonist, bevacizumab, axitinib, everolimus, cabozantinib, lenalidomide, lenvatinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, thalidomide, ziv-afibercept and vandetanib or any combination thereof. 78. The method of claim 75, wherein the anticancer agent comprises an adoptive cell therapy, wherein the adoptive cell therapy comprises T cells expressing a chimeric antigen receptor (CAR-T cells), NK cells expressing a chimeric antigen receptor (CAR-NK cells), any other immune cells expressing a chimeric antigen receptor, or any combination thereof. 79. The method of claim 75, wherein the anticancer agent (chemotherapy) comprises a topoisomerase inhibitor, a DNA methyltransferase inhibitor, a DNA intercalator, ixabepilone, bendamustine hydrochloride, eribulin mesylate, cabazitaxel, emtansine, trabectedin, nanoliposomal irinotecan, TAS-102, etoposide, carboplatin, cisplatin, doxorubicin, temozolomide or any combination thereof. 80. A method of treating a neuronal disease in a subject in need thereof, comprising administering to the subject the small interfering RNA of any one claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57. 81. The method of any one of claims 66 to 72 or 80, which further comprises administering an additional therapeutic agent to the subject. 82. The method of claim 81, wherein the additional therapeutic agent comprises an agent to treat a neuronal disease, wherein the agent comprises an acetylcholinesterase inhibitor, an NMDA antagonist, a dopamine supplement, a DOPA decarboxylase inhibitor, a Catechol- o-methyltransferase (COMT) inhibitor, a monoamine oxidase (MAO) inhibitor, an NMDA antagonist, an antioxidant, an antichorea drug, donepezil, rivastigmine, memantine, levodopa, carbidopa, benserazide, tolcapone, entacapone, selegiline, rasagiline, riluzole, edaravone, tetrabenazine or any combination thereof. 83. Use of the small interfering RNA of any one of claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57 for the manufacture of a medicament. 84. Use of the small interfering RNA of any one of claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57 for the manufacture of a medicament for the treatment of a cancer in a subject in need thereof. 85. Use of the small interfering RNA of any one of claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57 for the manufacture of a medicament for the treatment of a neuronal disease in a subject in need thereof. 86. The small interfering RNA of any one of claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57 for use in therapy. 87. The small interfering RNA of any one claims 1 to 54, the conjugate of claim 55 or 56, or the pharmaceutical composition of claim 57 for use in therapy of a cancer in a subject in need thereof. 88. The small interfering RNA of any one claims 1 to 54, the conjugate of claim 55 or 56, or the composition of claim 57 for use in therapy of a neuronal disease in a subject in need thereof. 89. The method of any one of claims 73 to 79, the use of claim 84, or the small interfering RNA for use of claim 87, wherein the cancer comprises a glioblastoma, glioblastoma multiforme, colorectal cancer, hepatocytoma, hepatoma, squamous cell carcinoma, small-cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), squamous NSCLC, nonsquamous NSCLC, glioma, gastrointestinal cancer, renal cancer, clear cell carcinoma, ovarian cancer, liver cancer, endometrial cancer, kidney cancer, renal cell carcinoma (RCC), prostate cancer, hormone refractory prostate adenocarcinoma, thyroid cancer, neuroblastoma, pancreatic cancer, cervical cancer, stomach cancer, bladder cancer, breast cancer, colon carcinoma, head and neck cancer, gastric cancer, germ cell tumor, pediatric sarcoma, sinonasal natural killer, melanoma, bone cancer, skin cancer, uterine cancer, cancer of the anal region, testicular cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, rectal cancer, solid tumors of childhood, cancer of the ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain cancer, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid cancer, squamous cell cancer, environmentally-induced cancers including those induced by asbestos, virus-related cancers or cancers of viral origin (e.g., human papilloma virus (HPV-related or -originating tumors)), an IDO1 expressing cancer, or any combinations thereof. 90. The method of claim 80, the use of claim 85, or the small interfering RNA for use of claim 88, wherein the neuronal disease comprises Alzheimer’s disease (AD), multiple system atrophy, Parkinson’s disease (PD), Parkinson's Disease Dementia (PDD), dementia with Lewy bodies, vascular and mixed dementia, Amytrophic Lateral Sclerosis (ALS) or any combinations thereof. 91. The method of claim 73 or 80, use of any one of claims 83 to 85, or small interfering RNA for use of any one of claims 86 to 88, wherein the subject is a human. 92. The method of claim 73 or 80, use of any one of claims 83 to 85, or small interfering RNA for use of any one of claims 86 to 88, wherein the subject is a mouse. 93. The method of claim 73 or 80, use of any one of claims 83 to 85, or small interfering RNA for use of any one of claims 86 to 88, wherein the subject is a rabbit. 94. The method of claim 73 or 80, use of any one of claims 83 to 85, or small interfering RNA for use of any one of claims 86 to 88, wherein the subject is a dog. 95. The method of claim 73 or 80, use of any one of claims 83 to 85, or small interfering RNA for use of any one of claims 86 to 88, wherein the subject is a non-human primate. 96. The method of any one of claims 73 or 80, the use of any one of claims 83 to 85, or the small interfering RNA for use of any one of claims 86 to 88, wherein the small interfering RNA, the conjugate, or the composition is administered orally, subcutaneously, parenterally, intrathecally, intra-cerebroventricularly, pulmonarily, topically, or intraventricularly. 97. A method of preparing a small interfering RNA capable of targeting both a murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript and a human indoleamine 2,3- dioxygenase 1 (IDO1) transcript comprising selecting a nucleic acid sequence within the murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript and the human indoleamine 2,3- dioxygenase 1 (IDO1) transcript and designing a contiguous nucleotide sequence of 14 to 22 nucleotides in length that is complementary to the nucleic acid sequence. 98. The method of claim 97, wherein the murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 3 and the human indoleamine 2,3-dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 1. 99. The method of claim 97 or 98, wherein the small interfering RNA comprises the nucleotide sequence set forth in SEQ ID NO: 16 to SEQ ID NO: 18. 100. A small interfering RNA prepared by the method of any one of claims 97 to 99. 101. A method of preparing a small interfering RNA capable of targeting both a non-human primate indoleamine 2,3-dioxygenase 1 (IDO1) transcript and a human indoleamine 2,3- dioxygenase 1 (IDO1) transcript comprising selecting a nucleic acid sequence within the murine indoleamine 2,3-dioxygenase 1 (IDO1) transcript and the human indoleamine 2,3- dioxygenase 1 (IDO1) transcript and designing a contiguous nucleotide sequence of 14 to 22 nucleotides in length that is complementary to the nucleic acid sequence. 102. The method of claim 101, wherein the non-human primate indoleamine 2,3-dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 13 and the human indoleamine 2,3-dioxygenase 1 (IDO1) transcript comprises SEQ ID NO: 1. 103. The method of claim 101 or 102, wherein the small interfering RNA comprises the nucleotide sequence set forth in SEQ ID NO: 15. 104. A small interfering RNA prepared by the method of any one of claims 100 to 103.