Inclusion Criteria: 1. Symptomatic disease due to osteoarthritis, defined as a WOMAC Pain score ≥ 8 (worst possible = 20) 2. Focused Analgesia Selection Test will be used to determine whether patients can report pain with sufficient consistency to enter the clinical trial 3. Males and females between 45 and 85 years of age, inclusive 4. Kellgren-Lawrence grading of 2 or 3 within the last 6 months 5. Stable analgesic regimen during the 4 weeks prior to enrollment 6. In the judgment of the Investigator, acceptable general medical condition 7. Life expectancy \>6 months 8. Male and female participants who are heterosexually active and not surgically sterile must agree to use effective contraception, including abstinence, for the duration of the study 9. Have suitable knee joint anatomy for intra-articular injection 10. Willing and able to return for the follow-up (FU) visits 11. Able to read and understand study instructions, and willing and able to comply with all study procedures Exclusion Criteria: 1. Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug, including double-stranded DNA, mannose, and sucrose 2. Previously received XT-150 injection(s) 3. Scheduled partial or complete knee replacement within 6 months; participant agrees not to schedule a knee replacement during Stage A of the study 4. History of knee arthroplasty on the Index Knee, i.e., selected for study injection(s) 5. History of rheumatoid arthritis or other inflammatory disease 6. History of immunosuppressive therapy; systemic steroids in the last 3 months 7. Received knee injection with hyaluronic acid or stem-cells in the last 6 months 8. Knee injection of glucocorticoid in the last 3 months 9. Current treatment with systemic immunosuppressive (systemic corticosteroid therapy or other strong immunosuppressant) 10. Currently receiving systemic chemotherapy or radiation therapy for malignancy 11. Clinically significant hepatic disease as indicated by clinical laboratory results ≥3 times the upper limit of normal for any liver function test (e.g., aspartate aminotransferase, alanine aminotransferase) 12. Severe anemia (Grade 3; hemoglobin \<8.0 g/dL, \<4.9 mmol/L, \<80 g/L; transfusion indicated), Grade 1 white cell counts (lymphocytes \<LLN - 800/mm\^3; \<LLN - 0.8 x 109 /L, neutrophils \<LLN - 1500/mm\^3; \<LLN - 1.5 x 109 /L), LLN=Lower Limit Normal Range 13. Positive serology for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus 14. Significant neuropsychiatric conditions; dementia, major depression, or altered mental state that in the opinion of the Investigator will interfere with study participation 15. Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical treatments) 16. Current anticoagulant or anti-platelet treatment (e.g., warfarin, heparins, factor X inhibitors, clopidogrel, prasugrel, ticagrelor, or dipyridamole). Low-dose (≤ 325 mg/day) aspirin is permitted 17. Known or suspected history of active alcohol or intravenous/oral drug abuse within 1 year before the screening visit 18. Use of any investigational drug or device within 3 months before enrollment or current participation in a trial that included intervention with a drug or device; or currently participating in an investigational drug or device study 19. Any condition that, in the opinion of the Investigator, could compromise the safety of the participant, the participant's ability to communicate with the study staff, or the quality of the data