Targeted mRNA delivery with bispecific antibodies that tether LNPs to cell-surface markers DOI Creative Commons

Bettina Dietmair,

James Humphries, Tim R. Mercer

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(2), P. 102520 - 102520

Published: March 20, 2025

Efficient delivery of mRNA-lipid nanoparticles (LNPs) to specific cell types remains a major challenge for mRNA therapeutics. Conventional targeting approaches involve modifying the lipid composition or functionalizing surface LNPs, which complicates manufacturing and alters nanoparticle size, charge, stealth, impacting their immunogenicity. Here, we present generalizable method targeted mRNA-LNP that uses bispecific antibodies (BsAbs) form bridge between LNPs markers. BsAbs can be combined with administered first, binding proteins on target cells later retaining unmodified in affected tissues. We demonstrate efficient cell-type-specific mRNA-LNPs beyond liver, epidermal growth factor receptor (EGFR)- folate hydrolase 1 (PSMA)-positive vitro vivo. The flexibility this technology, achieved by substituting cell-targeting region BsAbs, enables rapid development next-generation drugs.

Language: Английский

Targeted mRNA delivery with bispecific antibodies that tether LNPs to cell-surface markers DOI Creative Commons

Bettina Dietmair,

James Humphries, Tim R. Mercer

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(2), P. 102520 - 102520

Published: March 20, 2025

Efficient delivery of mRNA-lipid nanoparticles (LNPs) to specific cell types remains a major challenge for mRNA therapeutics. Conventional targeting approaches involve modifying the lipid composition or functionalizing surface LNPs, which complicates manufacturing and alters nanoparticle size, charge, stealth, impacting their immunogenicity. Here, we present generalizable method targeted mRNA-LNP that uses bispecific antibodies (BsAbs) form bridge between LNPs markers. BsAbs can be combined with administered first, binding proteins on target cells later retaining unmodified in affected tissues. We demonstrate efficient cell-type-specific mRNA-LNPs beyond liver, epidermal growth factor receptor (EGFR)- folate hydrolase 1 (PSMA)-positive vitro vivo. The flexibility this technology, achieved by substituting cell-targeting region BsAbs, enables rapid development next-generation drugs.

Language: Английский

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