Standard Bioconjugation Chemistry Comes with Hidden Traps for Targeted LNPs

A recent study (linked) reveals that standard bioconjugation methods (such as DBCO click chemistry and maleimide-thiol coupling) can activate the complement cascade, especially under background inflammation, triggering off-target uptake by lung phagocytes and acute systemic toxicity.
• DBCO induces surface-specific antibody aggregation.
• Unreacted maleimides trigger plasma albumin clustering

At Tiva Biosciences, we’ve alsoobserved that losing site specificity during binder conjugation can completely eliminate payload expression in T-cells. Robust tLNP development requires a strategic approach:
✅ Complement-conscious linker selection
✅ Surface-quenching & passivation
✅ Density & orientation optimization
✅ Comprehensive analytical characterization