Cytosolic delivery of inhibitory antibodies with cationic lipids.

Abstract:

:Antibodies can be developed to directly inhibit almost any protein, but their inability to enter the cytosol limits inhibitory antibodies to membrane-associated or extracellular targets. Developing a cytosolic antibody delivery system would offer unique opportunities to directly inhibit and study intracellular protein function. Here we demonstrate that IgG antibodies that are conjugated with anionic polypeptides (ApPs) can be complexed with cationic lipids originally designed for nucleic acid delivery through electrostatic interactions, enabling close to 90% cytosolic delivery efficiency with only 500 nM IgG. The ApP is fused to a small photoreactive antibody-binding domain (pAbBD) that can be site-specifically photocrosslinked to nearly all off-the-shelf IgGs, enabling easy exchange of cargo IgGs. We show that cytosolically delivered IgGs can inhibit the drug efflux pump multidrug resistance-associated protein 1 (MRP1) and the transcription factor NFκB. This work establishes an approach for using existing antibody collections to modulate intracellular protein function.

authors

Wang HH,Tsourkas A

doi

10.1073/pnas.1913973116

subject

Has Abstract

pub_date

2019-10-29 00:00:00

pages

22132-22139

issue

44

eissn

0027-8424

issn

1091-6490

pii

1913973116

journal_volume

116

pub_type

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