Исследования

Наши исследования built вокруг одной conviction: рак — evolutionary reversion, которую можно reverse у source. Lead платформа — NKG2D-LIF6 chimera.

NKG2D-LIF6 Chimera

2,123 bp · single construct · AAV9-deliverable

Chimeric receptor-effector construct, fusing human NKG2D extracellular domain (binds stress ligands MICA и MICB, selectively upregulated на solid tumor cells) с elephant LIF6 — re-functionalized pseudogene, mediating rapid mitochondrial apoptosis и объясняющий Peto's Paradox у слонов (Vazquez et al. 2018, Cell Reports).

Архитектура

Recognition module: NKG2D ECD (residues 79-216) — binds MICA/MICB tumor-stress ligands
Linker: Оптимизированный P2A self-cleaving peptide
Effector module: Codon-optimized elephant LIF6 с retained mitochondrial localization signal
Доставка: Single AAV9-encoded payload, IV administration

⚠ Stage disclosure: Каждое numerical или biological claim на этой странице — computational prediction. Сейчас отсутствуют in vivo data, human data, peer-reviewed публикация NKG2D-LIF6 chimera. Wet-lab validation начинается Q3–Q4 2026 across CRC, melanoma и pancreatic syngeneic murine tumor models. Methods и code будут open-sourced под CC BY 4.0 на github.com/nightbox-llc/chimera-design-notes.

In Silico Validation (computational only)

Predicted ~99% tumor growth inhibition ceiling на CRC models
Selectivity ratio > 10³ tumor vs. healthy tissue (modeled MICA/MICB expression atlas)
Folding stability confirmed в human cellular context (AlphaFold + Rosetta refinement)
Competitive intelligence scan: clean IP whitespace на specific chimera

Scientific Rationale

Большинство "elephant biology into therapy" проектов deliver TP53 — upstream sensor. Мы deliver LIF6 — downstream killer. TP53 — pleiotropic transcription factor с сотнями downstream targets и timing dependencies. LIF6 — single-purpose mitochondrial puncher с cleaner pharmacology и faster kill kinetics.

Fusing LIF6 к ligand-binding domain NKG2D — effector triggered только в клетках, exprezing stress signature, characteristic для solid tumors. Это обходит manufacturing complexity CAR-T while maintaining selectivity.

Открытые вопросы

NKG2D ligand shedding tumors как escape mechanism
On-target/off-tumor toxicity от NK и γδ T cell engagement
Folding behavior elephant LIF6 в human cellular context (long-term)
Optimal AAV serotype для solid tumor biodistribution

Researchers, clinicians, prospective collaborators: please reach out to artem@nightboxllc.com.