{"artifact":{"id":"experiment-exp-wiki-experiments-lrrk2-aav-gene-therapy-comparison","artifact_type":"experiment","entity_ids":null,"title":"Gene Therapy: AAV Serotype Comparison for LRRK2 Knockdown","quality_score":0.675,"created_by":"crosslink-v2","provenance_chain":null,"content_hash":null,"metadata":{"source":{"type":"manual","source_name":"wiki","extracted_by":"backfill_v1","extraction_date":"2026-04-16T01:00:16.902069Z"},"summary":"# Gene Therapy: AAV Serotype Comparison for LRRK2 Knockdown\n## Background and Rationale\nParkinson's disease (PD) is characterized by progressive neurodegeneration, with mutations in the LRRK2 gene representing one of the most common genetic causes. The G2019S mutation in LRRK2 leads to increased kinase activity and neuronal toxicity, making LRRK2 an attractive therapeutic target for gene therapy approaches. Adeno-associated virus (AAV) vectors have emerged as promising delivery systems for neuro","entities":{"genes":["AAV"],"diseases":["Parkinson's Disease"]},"model_system":"mouse","_schema_version":1,"experiment_type":"validation","primary_outcome":"Validate Gene Therapy: AAV Serotype Comparison for LRRK2 Knockdown","methodology_notes":"Phase 1 (Weeks 0-1): Genotype confirmation of LRRK2-G2019S transgenic mice (n=60, 8-10 weeks old). Randomize into 5 groups (n=12 each): AAV9-shLRRK2, AAV-PHP.eB-shLRRK2, AAV-DJ-shLRRK2, AAV2/5-shLRRK2, and control AAV-scrambled shRNA. Phase 2 (Week 2): Perform stereotactic injections of AAV vectors (2×10^12 vg/ml, 2μl per injection site) bilaterally into substantia nigra and striatum under isoflurane anesthesia. Monitor post-surgical recovery for 7 days. Phase 3 (Weeks 3-8): Conduct weekly behavioral assessments including rotarod performance (accelerating 4-40 rpm over 5 minutes), cylinder test for forelimb asymmetry, and open field locomotor activity. Phase 4 (Week 6): Sacrifice subset of mice (n=4 per group) for early timepoint analysis. Collect brain tissue for biodistribution analysis via qPCR using serotype-specific primers. Phase 5 (Week 9): Perform final behavioral testing battery. Sacrifice remaining mice and harvest brains. Process tissues for Western blotting (LRRK2, tyrosine","replication_status":"replicated","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.902074","needs_review":true,"extraction_notes":"Backfilled from wiki source (no PMID available)","extraction_confidence":0.4}},"created_at":"2026-04-02T10:01:41.825940-07:00","updated_at":"2026-04-16T01:00:16-07:00","version_number":4,"parent_version_id":null,"version_tag":null,"changelog":null,"is_latest":1,"lifecycle_state":"active","superseded_by":null,"deprecated_at":null,"deprecated_reason":null,"dependencies":null,"market_price":0.5,"origin_type":"internal","origin_url":null,"lifecycle_changed_at":"2026-04-02T10:01:41.825940-07:00","citation_count":0,"embed_count":0,"derivation_count":0,"support_count":0,"contradiction_count":0,"total_usage":0.0,"usage_score":0.5,"usage_computed_at":null,"quality_status":"ok","contributors":[],"answers_question_ids":null,"deprecated_reason_detail":null,"deprecated_reason_code":null,"commit_sha":null,"commit_submodule":null,"last_mutated_at":"2026-05-16T14:51:34.657673-07:00","disputed_at":null,"gap_id":null,"mission_id":null,"intrinsic_priority":null,"effective_priority":null,"artifact_id":"0ac6140a-b7d5-4bef-b545-f01a0819d288","artifact_dir":null,"primary_filename":null,"accessory_filenames":null,"folder_layout_version":1,"migrated_to_folder_at":null,"hypothesis_id":null,"authorship":{"kind":"human","contributors":[{"role":"author","actor_ref":"crosslink-v2"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[{"target_artifact_id":"wiki-therapeutics-bbb-penetrant-antibodies","link_type":"related","strength":0.63,"evidence":"Reverse: 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