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

Inclusion Criteria:

1. Signed ICF;

2. Aged 18 to 65 years old;

3. Primary open Angle glaucoma (POAG) with elevated intraocular pressure (IOP) wasdiagnosed with ≥1 year medical history record ;

4. Good function level of organs;

5. Good compliance and willing to comply with the visit schedule, laboratory tests andother specified test etc. per protocol;

6. 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 acombination 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 acombination therapy of 2 or more drugs lowering IOP;

• Both eyes have a Shaffer Angle mirror rating greater than 3.

Exclusion Criteria:

1. Secondary glaucoma;

2. Any active or recurrent intraocular infection or inflammation, including but notlimited to uveitis;

3. The target intervenning eye has severe xerophthalmia or clinically significantactive corneal disease;

4. Any condition no accepting the measure of IOP;

5. 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;

6. Any of hepatitis B virus (HBV) HbsAg or HBV-DNA, hepatitis C virus (HCV) HCAb, orepstein-barr virus (EBV), or cytomegalovirus (CMV) nucleic acid test is positive;

7. Severe active bacterial, viral, fungal, malaria or parasitic systemic infection;

8. Any past or present malignancy, myeloproliferative or immunodeficient disease;

9. History of major organ diseases or abnormalities in laboratory tests, including:

10. Liver cirrhosis, liver fibrosis or active hepatitis, and/or abnormal liverfunction 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);

11. Cardiovascular and cerebrovascular diseases, including uncontrolledhypertension, myocardial infarction, myocarditis, arrhythmia, stroke, etc.;

12. Kidney disease, or creatinine ≥ 1.5ULN and creatinine clearance < 30% normallevel (using the Cockcroft-Gault equation);

13. Endocrine disorders, such as insulin-dependent diabetes mellitus,hyperthyroidism or hypothyroidism;

14. Severe pulmonary hypertension, chronic obstructive pulmonary disease,interstitial pneumonia;

15. Any severe psychiatric disorders;

16. Participating in another clinical study of a drug or device, or administrated theinvestigational drug within 42 days prior to the screening visit;

17. Pregnant or lactating women;

18. Refusing to accept any contraception measures;

19. Allergic to clinical investigational drugs or their excipients;

20. Other conditions assessed by the investigator as unsuitable for participation inthis study.

Special Exclusion Criteria for Group 2:

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

• A history of anterior chamber angle stenosis, congenital glaucoma, or angle closure,clinically significant anterior peripheral adhesion, or extensive cicatricialadhesion caused by surgery/laser therapy in the anterior chamber angle;

• The central corneal thickness is less than 480 μm or more than 620 μm.