A Clinical Trial Evaluating the Safety and Efficacy of Intravenous HNF4α SrRNA in Treating Metastatic CRC Patients

Inclusion Criteria: 1. Males or females, aged 18 years or older. 2. Patients with histologically confirmed colorectal cancer that has been determined to be unresectable or metastatic. 3. Colorectal cancer subjects who are unsuitable or unable to tolerate standard systemic therapy, or who have received standard systemic therapy but have disease progression based on RECIST (version 1.1) criteria, including chemotherapy based on fluorouracil, oxaliplatin, or irinotecan, and targeted therapies with anti-VEGF/EGFR monoclonal antibodies. 4. Patients with confirmed deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) in tumor tissue, who have been treated with immune checkpoint inhibitors (anti-PD-1 or anti-PD-L1 antibodies) and are assessed with disease progression. 5. According to the RECIST (version 1.1) criteria, there are measurable target lesions suitable for repeated measurements for assessment. 6. Life expectancy of 12 weeks or more. 7. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2. 8. Males with fertility and females of childbearing potential are willing to use a highly effective method of contraception for the entire study period and for 6 months after study drug discontinuation. Females of childbearing age, including premenopausal females and within 2 years after menopause, must have a negative serum pregnancy test result within 7 days prior to the first dose of study treatment. 9. Subjects who had a voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol. Exclusion Criteria: * Patients with any of the following criteria were excluded from participation in this study 1. Patients who have undergone standard adjuvant chemotherapy after tumor resection, and have experienced recurrence or metastasis within 6 months after discontinuing the medication, and have not received standard systemic therapy. 2. Clinical or imaging indications suggest the current presence of intestinal obstruction, perforation, or bleeding; or those who, upon investigator assessment, are at a higher risk of perforation or bleeding. 3. Inadequate liver function：serum bilirubin \> 3 × the upper limit of normal (ULN), or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine aminotransferase (ALT) \> 5 × ULN. 4. Inadequate renal function defined as creatinine \>1.5 × ULN or calculated creatinine clearance \< 40 mL/min. 5. Absolute neutrophil count (ANC) \< 1.5×109/L, or Platelets \< 50×109/L, or Hemoglobin \< 9.0 g/dL. 6. International normalized ratio (INR) \> 2.0. 7. Patients with confirmed tumor brain metastases. 8. Poorly controlled hypertension, diabetes or other serious heart or lung diseases, or with serious dysfunction. 9. Patients who have received local or systemic anti-tumor treatments such as immunotherapy, targeted therapy, and chemotherapy within 4 weeks, or radiation therapy within 3 weeks, except for treatment regimens assessed as disease progression according to RECIST v1.1. 10. All toxicities related to prior locoregional or systemic anti-tumor treatments are still grade 2 or more (except for hair loss and other events that have been judged tolerable by researchers). 11. Uncontrolled active infection (eg, lung infections, or abdominal infections). 12. History of malignancy other than CRC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate \> 90%), such as adequately treated early gastric carcinoma, carcinoma in situ of the cervix, non-melanoma skin carcinoma, or localized prostate cancer. 13. Having an active autoimmune disease that requires systemic treatment within the past 2 years. 14. Any condition requiring systemic treatment with corticosteroids (prednisone or equivalent \>10mg/day) or other immunosuppressive drugs within 14 days prior to the first administration of the investigational drug. 15. Patients with a history of organ transplantation. 16. Hepatitis B virus DNA greater than 500 IU/ml, or hepatitis C virus RNA greater than 100 IU/ml. 17. Positive for human immunodeficiency virus (HIV). 18. Pregnant/lactating women, or women with the possibility of pregnancy. 19. Individuals who have participated in other drug trials within 4 weeks. 20. Other conditions deemed unsuitable for participation in this clinical trial by the investigator.