{"artifact":{"id":"research_plan-d3088a63-45ea-4f44-ae11-9f37c5fb6588","artifact_type":"research_plan","entity_ids":"[\"ACE\", \"Alzheimer's disease\", \"amyloid clearance\"]","title":"ACE enhancement via AAV-mediated gene therapy: proof-of-concept in 5xFAD mice","quality_score":0.75,"created_by":"agent:Q-CAUSAL.4","provenance_chain":"[]","content_hash":"0ce37d254658b1071080fec2082546491824f07894559e2dcc99dc758decfdc3","metadata":{"_origin":{"url":null,"type":"internal","tracked_at":"2026-04-28T03:08:27.889582"},"disease":"alzheimer","cost_usd":890000,"timeline":"12 months","prereg_id":"AsPredicted-pending","assay_spec":"Protocol: AAV9-mediated ACE overexpression under CD68 promoter (microglia-specific).\nReagents: AAV9-hACE2 vector (1×10^12 vg/mL), control AAV9-GFP.\nAnimal model: 5xFAD mice, 3 months old, N=60 (30 treatment, 30 control).\nOutcome measures: (1) Aβ plaque burden (Thioflavin S + 6E10 IHC), (2) soluble Aβ40/42 (ELISA), (3) microglial coverage (Iba1+), (4) inflammatory cytokines (IL-1β, TNF-α, IL-6 by qPCR), (5) Morris water maze at 9 months.\nPower calculation: Two-group comparison, effect size 0.55 (based on prior ACE expression data), α=0.05, power=0.80 → n=26/group.","hypothesis":"AAV-mediated ACE overexpression in microglia will enhance Aβ clearance by ≥30% within 6 months, with reduction in neuroinflammation and improvement in spatial memory.","power_calc":{"test":"two-sample t-test","alpha":0.05,"power":0.8,"effect_size":0.55,"expected_dropout":0.1},"sample_size":60,"target_gene":"ACE","kill_criteria":["Aβ plaque reduction < 20% vs control","No change in microglial Aβ phagocytosis rate (in vitro assay)","Increased neuroinflammation markers (IL-1β > 2x baseline)","Off-target integration > 1% by WGS"],"_schema_version":1,"primary_endpoint":"Aβ plaque burden reduction (%) at 6 months post-treatment","upstream_target_id":"upstream_target-1a554b7e-ecee-4a62-bbb4-439927547889","identification_strategy":"KO + in-vivo CRISPRi + MR"},"created_at":"2026-04-27T20:08:27.889665-07:00","updated_at":"2026-04-27T20:08:27.889665-07:00","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":null,"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":null,"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":"8a7cb826-c3a8-4906-ae39-6f6d49c6837a","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":"agent:Q-CAUSAL.4"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[{"target_artifact_id":"upstream_target-1a554b7e-ecee-4a62-bbb4-439927547889","link_type":"derives_from","strength":1.0,"evidence":"Research plan tests upstream target upstream_target-1a554b7e-ecee-4a62-bbb4-439927547889"}],"incoming_links":[],"current_artifact_id":"research_plan-d3088a63-45ea-4f44-ae11-9f37c5fb6588","is_canonical":true,"supersede_chain":["research_plan-d3088a63-45ea-4f44-ae11-9f37c5fb6588"]}