Safety of Intra-Articular Sc-rAAV2.5IL-1Ra in Subjects With Moderate Knee OA

Inclusion Criteria:

- Age 18-65 years

- Gender: both males and females

- Target disease: Moderate OA of the knee

- Persistent symptoms, despite standard NSAID

- Normal limits for the following:

- Complete blood count

- Prothrombin Time, Activated partial thromboplastin time

- Blood chemistry (Glucose, Na, K, Cl, CO2, BUN, creatinine, Ca, PO4, magnesium, uric
acid)

- Liver function tests (amylase, total bilirubin, alkaline phosphate, GGT, AST, ALT,
total protein, albumin)

- Able and willing to return to the Mayo Clinic for follow-up visits, as required by
this study

- Able undergo MRI of the knee

- Subjects should be able to give appropriate consent or have an appropriate
representative available to do so.

- Potential subjects should have failed a three-month trial of a minimum of two
conservative therapies before being considered for this trial. These conservative
therapies include: activity modification, weight loss, physical therapy, and
anti-inflammatory or injection therapy.

Exclusion Criteria:

- Pregnant, or currently breast-feeding

- Ongoing infectious disease including HIV, HTLV, hepatitis, syphilis or tuberculosis
positive

- Individuals who have OA as part of another syndrome (e.g. Ehler's Danlos, Stickler
syndrome, etc.)

- Systemic, rheumatic or inflammatory disease of the knee or chondrocalcinosis,
hemochromatosis, inflammatory arthritis, arthropathy of the knee associated with
juxta-articular Paget's disease of the femur or tibia, ochronosis, hemophilic
arthropathy, infectious arthritis, Charcot's knee joint, villonodular synovitis, and
synovial chondromatosis.

- Clinically significant cardiovascular, renal, hepatic, endocrine disease, diabetes,
cancer, autoimmune diseases; a serious infection or major operation within 30 days of
enrollment; a history of psychiatric disease or recent history of alcoholism or drug
addiction.

- Currently taking immunosuppressant medications

- Anticipated major surgery during the study period.

- Individuals involved in another protocol, or have been treated under one within the
last 3 months.

- Intra-articular therapy in the index knee within the previous 6 months.

- Surgery to the target knee within 6 months prior to screening.

- Surgery to other weight bearing joints if it will interfere with knee assessments

- Prior articular transplant procedures

- Prior reconstruction surgery to the target knee within 12 months

- X-ray findings of acute fractures

- Known severe loss of bone density, and/or severe bone or joint deformity in the target
knee.

- Knee pain associated with patella-femoral arthritis or chondromalacia in the target
knee.

- Significant target knee infection or overlying skin disorder/infection within the
previous 6 months prior to study enrollment

- Require cane or other assistive device for walking

- Symptomatic OA of the hips, spine or ankle if it would interfere with the evaluation
of the target knee,

- History of documented nerve damage in the affected limb, or vascular insufficiency,

- Condition requiring use of systemic steroids,

- Coagulation disorder.

- Patients with unstable knees

- Temperature above 99.5 F.

- Elevated liver transaminases

- Identification as a member of a vulnerable population.

- BMI greater than 40.

- History of allergy to local anesthetics

- Currently taking anti-rheumatic disease medication (including methotrexate or other
antimetabolites) within the 3 months prior to entry in the study.