CRISPR/Cas9 Instantaneous Gene Editing Therapy to Intraocular Hypertensive POAG With MYOC Mutation

Prior treatment

• Participating in another clinical study of a drug or device, or administrated the investigational drug within 42 days prior to the screening visit;
• Allergic to clinical investigational drugs or their excipients;

Other illness

• Any active or recurrent intraocular infection or inflammation, including but not limited to uveitis;
• The target intervenning eye has severe xerophthalmia or clinically significant active corneal disease;
• Any condition no accepting the measure of IOP;
• Any positive of human immunodeficiency virus type 1/2 (HIV-1/HIV-2) antibody, treponema pallidum (TP) specific antibody, human T-lymphotropic virus type 1 or 2 (HTLV-1/HTLV-2) antibody, or vesicular stomatitis virus G (VSV-G) antibody;
• Any of hepatitis B virus (HBV) HbsAg or HBV-DNA, hepatitis C virus (HCV) HCAb, or epstein-barr virus (EBV), or cytomegalovirus (CMV) nucleic acid test is positive;
• Severe active bacterial, viral, fungal, malaria or parasitic systemic infection;
• Any past or present malignancy, myeloproliferative or immunodeficient disease;
• Any severe psychiatric disorders;
• Other conditions assessed by the investigator as unsuitable for participation in this study.
  • Special Exclusion Criteria for Group 2:
• A history of anterior chamber angle stenosis, congenital glaucoma, or angle closure, clinically significant anterior peripheral adhesion, or extensive cicatricial adhesion caused by surgery/laser therapy in the anterior chamber angle;

Lab values

• History of major organ diseases or abnormalities in laboratory tests, including:
  • Liver cirrhosis, liver fibrosis or active hepatitis, and/or abnormal liver function tests (serum total bilirubin (TBIL) ≥1.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥2.5×ULN; Alkaline phosphatase ≥2.5 × ULN);
  • Cardiovascular and cerebrovascular diseases, including uncontrolled hypertension, myocardial infarction, myocarditis, arrhythmia, stroke, etc.;
  • Kidney disease, or creatinine ≥ 1.5ULN and creatinine clearance \< 30% normal level (using the Cockcroft-Gault equation);
  • Endocrine disorders, such as insulin-dependent diabetes mellitus, hyperthyroidism or hypothyroidism;
  • Severe pulmonary hypertension, chronic obstructive pulmonary disease, interstitial pneumonia;

Age

• Retinal diseases: complicated with unexplained quadrant blindness, neovascularization age-related macular degeneration, retinal branch vein obstruction, central retinal vein obstruction, cystoid macular edema, macular hiatal hole and central serous retinopathy;

Other

• Secondary glaucoma;
• Pregnant or lactating women;
• Refusing to accept any contraception measures;
• The central corneal thickness is less than 480 μm or more than 620 μm.

• Signed ICF;
• Aged 18 to 65 years old;
• Primary open Angle glaucoma (POAG) with elevated intraocular pressure (IOP) was diagnosed with ≥1 year medical history record ;
• Good function level of organs;
• Good compliance and willing to comply with the visit schedule, laboratory tests and other specified test etc. per protocol;
• Agreeing to accept a long-term safety follow-up after 1 year of study.
  • Special Inclusion Criteria for Group 1:
• Target intervenning eye is no visual acuity;
• The intraocular pressure (IOP) was ≤35 mmHg and \> 21 mmHg after receiving a combination therapy of 2 or more drugs lowering IOP.
  • Special Inclusion Criteria for Group 2:
• MYOC gene mutation was detected in peripheral blood nucleated cells ;
• The intraocular pressure (IOP) was ≤30 mmHg and \> 21 mmHg after receiving a combination therapy of 2 or more drugs lowering IOP;
• Both eyes have a Shaffer Angle mirror rating greater than 3.