DNA Vaccine Therapy in Treating Patients With Chronic Hepatitis C Virus Infection

Inclusion Criteria:

* PRE-REGISTRATION INCLUSION CRITERIA
* Presence of active, chronic HCV infection confirmed by positive HCV RNA
* Willingness to use adequate contraception to avoid pregnancy or impregnation for the duration of study participation; Note:

  * The effects of INO-8000 with or without INO-9012 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  * For men and women who are not postmenopausal (i.e., \>= 12 months of non-therapy-induced amenorrhea, confirmed by follicle stimulating hormone \[FSH\], if not on hormone replacement) or surgically sterile (vasectomy in males or absence of ovaries and/or uterus in females), agreement to remain abstinent or use highly effective or combined contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and at least through week 12 after last dose
  * Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception
  * Examples of contraceptive methods with an expected failure rate of \< 1% per year include male sterilization and hormonal implants; alternatively, proper use of combined oral or injected hormonal contraceptives and certain intrauterine devices or two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of \< 1% per year (barrier methods must always be supplemented with the use of a spermicide)
  * Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
  * Should a female partner of a male study participant become pregnant while the male participant is on study, the male participant should inform his study physician immediately
* Willingness to avoid excessive use of alcohol during the study; note: excessive use is defined as drinking \>= 8 alcoholic drinks per week on average
* Willingness to provide blood samples for research tests specified in the protocol
* Ability to understand and willingness to sign a written informed consent document
* REGISTRATION INCLUSION CRITERIA
* Serum or plasma HCV RNA level \>= 10,000 IU/mL
* Screening HCV genotype, demonstrating genotype 1
* Alpha feto protein (AFP) levels within normal institutional limits or judged to be not clinically significant by the investigator; Exception: If deemed clinically significant, then liver imaging must be available within previous 6 months (e.g., ultrasound, computed tomography \[CT\] scan, magnetic resonance imaging \[MRI\]) showing no evidence of hepatocellular carcinoma
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Screening laboratory values (serum chemistry, hematology, prothrombin time \[PT\](international normalized ratio \[INR\])/activated partial thromboplastin time \[APTT\], and creatine phosphokinase \[CPK\]) obtained up to 45 days prior to administration of first vaccine injection on day 0 within institutional normal range or judged to be not clinically significant by principal investigator (PI) and medical monitor
* 12-lead electrocardiogram (ECG) showing normal heart rhythm; note: if there are abnormalities, then the abnormalities must be deemed of no clinical significance

Exclusion Criteria:

* PRE-REGISTRATION EXCLUSION CRITERIA
* Failure of previous HCV therapies
* Human immunodeficiency virus (HIV) infection
* Any previous treatment for HCV =\< 6 months prior to registration
* Other uncontrolled immune-compromising illness
* Autoimmune disorders, transplant recipients, other immunosuppression including any concurrent condition requiring the use of immunosuppressive/ immunomodulating agents; Exception: eye drop-containing and infrequent inhaled corticosteroids are permissible; topical corticosteroids are permissible at locations other than the administration site (upper arm); Note: All systemic corticosteroids must be discontinued at least 4 weeks prior to randomization; inhaled corticosteroids must be discontinued \>= 48 hours prior to randomization and courses of more than 2 weeks are not permissible within 4 weeks of randomization
* Ongoing hepatitis B virus (HBV) infection
* Documented evidence of fibrosis or cirrhosis (Metavir 2, 3, and 4) and subjects with significant extrahepatic manifestations of hepatitis C (such as cryoglobulinemia with symptoms or evidence of end-organ manifestations, renal disease, type 2 diabetes, or porphyria cutanea tarda
* Other known causes of significant liver disease including chronic or acute hepatitis B, acute hepatitis A, hemochromatosis, or homozygote alpha-1 antitrypsin deficiency
* Active malignancy; exception: non-melanoma skin cancers cancer(s) for which diagnosis and treatment was completed \>= 3 years prior to pre-registration
* History of major organ transplantation with an existing functional graft
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* History of cardiac arrhythmia, controlled or uncontrolled, including ventricular and supraventricular arrhythmia
* Pregnant or nursing women; Note: Pregnant women are excluded from this study because INO-8000 has an unknown potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with this DNA vaccine, breastfeeding should be discontinued if the mother is treated with INO-8000
* Current diagnosis or history of cardiac pre-excitation syndromes (e.g. Wolff-Parkinson-White)
* Metal implants on same limb as intended administration site
* Tattoos, scars, active lesions, or rashes =\< 2 cm of the intended site of study treatment
* Documentation of history of seizure within previous 5 years
* Pacemaker or other implanted device
* Any condition that, in the clinical judgement of the investigator, would place a participant at unreasonably increased risk
* REGISTRATION EXCLUSION CRITERIA
* Receiving any other investigational agents =\< 6 months prior to Registration
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to INO-8000 and INO-9012