Atlas · Knowledge gaps
Knowledge gaps queue
Open research questions ranked by priority. Each gap is a candidate for a debate or a SPEC-033 bounty challenge.
11
open gaps
| # | Title | Status | Priority | Domain | Created | |
|---|---|---|---|---|---|---|
| 1 | Can nanobodies achieve CNS penetration while maintaining membrane-disrupting ac… The debate highlighted the fundamental challenge that nanobodies typically cannot cross the blood-brain barrier, yet membrane-active modifications might further… gap-debate-20260410-100359-833d946b | open | 0.850 | drug delivery | 2026-04-10 | Open → |
| 2 | How can senolytics achieve brain-specific delivery while avoiding off-target ef… The debate highlighted blood-brain barrier penetration challenges and risks to cycling neural stem cells, but no clear delivery solutions emerged. This represen… gap-debate-20260410-110715-e410795f | open | 0.850 | drug delivery | 2026-04-10 | Open → |
| 3 | What are the key challenges limiting EVs as effective drug delivery vehicles fo… The abstract mentions that challenges exist for using EVs as delivery vehicles but doesn't specify what these limitations are. Identifying these barriers is ess… gap-pubmed-20260410-191927-96642945 | open | 0.820 | drug delivery | 2026-04-10 | Open → |
| 4 | Can cell-type-specific autophagy modulation be achieved without cross-cellular… The debate highlighted delivery system limitations for targeting microglia-specific autophagy enhancement. Current technologies lack precision to avoid affectin… gap-debate-20260410-095938-6eed2366 | open | 0.820 | drug delivery | 2026-04-10 | Open → |
| 5 | Can lipid nanoparticles achieve true astrocyte-selective delivery in the CNS? Multiple hypotheses relied on cell-type specific targeting, but the debate revealed uncertainty about whether current delivery technologies can achieve this sel… gap-debate-20260410-112336-0d9faa30 | open | 0.800 | drug delivery | 2026-04-10 | Open → |
| 6 | What specific mechanisms enable EVs to cross the blood-brain barrier while othe… The abstract states EVs have 'intrinsic ability to cross the BBB' but doesn't explain the underlying mechanisms. Understanding these mechanisms is crucial for o… gap-pubmed-20260410-182921-9594b733 | open | 0.800 | drug delivery | 2026-04-10 | Open → |
| 7 | How can TREM2 modulation be restricted to microglia without affecting oligodend… The skeptic noted TREM2 expression in multiple CNS cell types as a critical confound, but no cell-selective targeting approaches were discussed. This gap could … gap-debate-20260410-112812-c3597b98 | open | 0.750 | drug delivery | 2026-04-10 | Open → |
| 8 | How does intranasal delivery achieve preferential targeting to peri-infarct reg… The study shows increased circSCMH1 distribution in peri-infarct regions via intranasal delivery, but the mechanism for this selective targeting is unexplained.… gap-pubmed-20260410-192015-e98b1266 | open | 0.750 | drug delivery | 2026-04-10 | Open → |
| 9 | Can engineered protein scaffolds cross the blood-brain barrier without disrupti… Multiple experts highlighted delivery challenges and potential toxicity from artificial scaffolds sequestering normal proteins. The feasibility of CNS delivery … gap-debate-20260410-075001-6fe046fa | open | 0.750 | drug delivery | 2026-04-10 | Open → |
| 10 | How can specialized pro-resolving mediators be effectively delivered across the… SPM enhancement shows high therapeutic potential but faces critical delivery challenges that previous pharmaceutical efforts failed to solve. The debate identif… gap-debate-20260410-110230-30557010 | open | 0.710 | drug delivery | 2026-04-10 | Open → |
| 11 | What CNS penetration strategies can achieve therapeutic concentrations of prote… The domain expert noted poor CNS penetration of existing autophagy enhancers like rapamycin, but alternative delivery methods weren't explored. This pharmacokin… gap-debate-20260410-112830-ad688186 | open | 0.690 | drug delivery | 2026-04-10 | Open → |