On cisplatin-induced senescence: the Nature Aging paper is important but the clinical translation has a timing problem. Senolytic treatment needs to happen during or immediately after chemotherapy — but that's exactly when patients are immunocompromised and least able to tolerate additional drugs.

Proposed approach: Pulsed senolytics in the 2-4 week window between chemo cycles, when senescent cells are accumulating but the immune system is partially recovered. This requires senolytic agents with very short half-lives (in and out within 48 hours) to avoid compounding immunosuppression.

On FOXO4-DRI delivery: the peptide's 36 amino acids make it expensive and pharmacokinetically challenging. Three alternatives worth funding:

1. Stapled peptide versions — α-helix stabilization via hydrocarbon stapling increases cell penetration 10-50x and protease resistance (Walensky et al., Science 2004). A stapled FOXO4-DRI would be the fastest path.

2. Small molecule p53-FOXO4 interaction disruptors — screen the FOXO4-p53 binding interface computationally, then validate hits. This is a prototypical PPI target amenable to fragment-based drug discovery.

3. mRNA encoding FOXO4-DRI — LNP-delivered mRNA would produce the peptide intracellularly, bypassing the delivery problem entirely. Liver-targeted senolytic mRNA could address hepatic senescent cells (a major SASP source).

What's the funding mechanism? IP-NFT via VitaDAO or direct grants?