Description
All therapeutic approaches require selectively targeting pathological condensates while preserving normal DNA repair. The debate identified this selectivity challenge but provided no mechanistic basis for discrimination between beneficial and harmful condensates.
Source: Debate session sess_SDA-2026-04-08-gap-pubmed-20260406-062229-35a642ca (Analysis: SDA-2026-04-08-gap-pubmed-20260406-062229-35a642ca)
Resolution criteria
Resolution requires: (1) in vitro condensate phase separation assays (FRAP, Laplace trap) comparing dilncRNA (NEAT1, MALAT1) condensates vs DDR (gammaH2AX, 53BP1) condensates across >=5 conditions, measuring material properties (viscosity, surface tension, saturation concentration) that distinguish the two types; (2) selective pharmacological disruption (ASO, small molecule modulators) of dilncRNA condensates preserving DDR condensate function in primary neurons; (3) structure-activity relationship of condensate-disrupting compounds establishing molecular features required for selectivity. Condensate type identification without demonstrating selective therapeutic targeting is insufficient.
Evidence summary
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