A Safety and Efficacy Study of TALEN and CRISPR/Cas9 in the Treatment of HPV-related Cervical Intraepithelial NeoplasiaⅠ

Sun Yat-sen University

Status and phase: Unknown; Phase 1

Conditions: Human Papillomavirus-Related Malignant Neoplasm

Treatments: Biological: CRISPR/Cas9; Biological: TALEN

Study type: Interventional

Funder types: Other

Identifiers

NCT03057912

2017CRISPR/Cas9&TALEN

Details and patient eligibility

About

This is an open-label and triple cohort study of the safety and efficacy of TALEN and CRISPR/Cas9 to possibly treat HPV Persistency and human cervical intraepithelial neoplasiaⅠwithout invasion.

Full description

HPV persistent infection is the major causal factor of cervical intraepithelial neoplasia (CIN) and cervical cancer. The important roles of E6 and E7 playing in HPV-driven carcinogenesis make them attractive targets for therapeutic interventions. Previous evidences showed that using designated TALEN and CRISPR/Cas9 as genome editing tool could produce disruption of HPV16 and HPV18 E6/E7 DNA, significantly decreasing the expression of E6/E7, inducing cell apoptosis and inhibiting cell lines growth.

This study will evaluate the safety and efficacy of TALEN-HPV E6/E7 and CRISPR/Cas9-HPV E6/E7 in treating HPV Persistency and HPV-related Cervical Intraepithelial NeoplasiaⅠ

Enrollment: 60 estimated patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented HPV16 or HPV18 infection.
• Married and fertile, no fertility requirements.
• Without administration of hormone in the last six months.
• Subjects must be meet the ethical requirements and have signed informed consent.

Exclusion criteria

• Pregnancy and breast feeding
• Any bacterial vaginitis
• Any Fungal vaginitis
• Any sexually transmitted diseases
• Active drug or alcohol abuse
• Any HPV medications within the past 12 weeks
• Allergy to active or non active ingredients in the study of drugs
• Cardiac insufficiency
• Liver and renal insufficiency
• Hypertension and severe complications
• Serious illness in past 30 days
• Currently participating in another clinical trial or any prior gene therapy

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups

TALEN

Experimental group

Description:

TALEN (TALEN-HPV16 E6/E7 or TALEN-HPV18 E6/E7) plasmid in gel, administered twice one week for 4 weeks.

Treatment:

Biological: TALEN

CRISPR/Cas9

Experimental group

Description:

CRISPR/Cas9 (CRISPR/Cas9-HPV16 E6/E7T1 or CRISPR/Cas9-HPV18 E6/E7T2 ）plasmid in gel, administered twice one week for 4 weeks.

Treatment:

Biological: CRISPR/Cas9

Control group

No Intervention group

Description:

Observation