Exploratory Study on mRNA Therapy Targeting CD19 for the Treatment of Refractory Autoimmune Diseases

Inclusion criteria

• 1. Age range of 14-70 years old (including threshold), gender not limited;
• 2. KPS score>60 points, life expectancy greater than 6 months;
• 3. Male and female patients of appropriate age must use reliable methods of contraception before entering the trial, during the research process until 30 days after discontinuation of medication; Reliable contraceptive methods will be determined by the primary researchers or designated personnel;
• 4. Those who can understand this experiment and have signed the informed consent form.
• 5. Before screening (at baseline), corresponding conditions should be met;
• 6. Indications for severe, recurrent, or refractory immune related diseases, including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), systemic lupus erythematosus（SLE），systemic sclerosis （SSc） etc., meet the corresponding inclusion criteria; For other types of diseases, researchers will assess whether they meet the inclusion requirements after fully evaluating the risks and benefits based on the patient's treatment needs.

Exclusion criteria

• 1) Study participants who are allergic or hypersensitive to any component of the investigational drug, including those who are allergic to messenger RNA (mRNA) vaccines or other RNA LNP products.
• 2) Merge any active infections that require antibiotic treatment and have not been controlled for at least one week prior to D1 administration.
• 3) Malignant tumors diagnosed within the first 2 years of screening are excluded, except for skin basal cell carcinoma, squamous cell carcinoma, or cervical cancer in situ that has been adequately treated.
• 4) Uncontrolled ischemic heart disease, including unstable angina within the previous 6 months of screening, or evidence of active ischemic heart disease on electrocardiogram.
• 5) New York Heart Association (NYHA) grade III-IV heart failure.
• 6) Study participants with combined active hepatitis B virus (HBV) infection [defined as surface antigen (HBsAg) positive and HBV DNA positive (detected by PCR)].
• 7) Study participants with combined active hepatitis C virus (HCV) infection (defined as HCV RNA positive (detected by PCR), regardless of anti HCV antibody status).
• 8) Human immunodeficiency virus (HIV) infection or history of HIV infection.
• 9) Study participants who tested positive for Treponema pallidum specific antibodies.
• 10) There may be active infection of Mycobacterium tuberculosis.
• 11) Women who are currently pregnant, breastfeeding, or planning to become pregnant.
• 12) Combining severe or recently (<2 months) diagnosed medical conditions, as determined by the researchers, may affect the study participants' tolerance to the study drug or their ability to complete the study process.
• 13) Received attenuated live vaccine or protein subunit vaccine within 30 days prior to the first study medication.