Work

Delivery of mRNA encoding an anti‐tau monoclonal antibody and engineered scFv intrabody results in functional antibody expression in neurons

Year: 2024

Type: article

Abstract: BACKGROUND: Monoclonal antibodies have emerged as a leading therapeutic agent for the treatment of disease, including Alzheimer's disease. Such antibodies, however, are expensive and timely to produce and require frequent dosing regimens to ensure disease-modifying effects. Synthetic in vitro-transcribed mRNA encoding antibodies presents a promising alternative to conventional passive immunotherapy and overcomes the need to generate recombinant antibodies. METHOD: In vitro-transcribed (IVT) mRNA encoding a tau specific antibody as a full-sized IgG and as a single chain variable fragment (scFv) was synthesised. Human neuroblastoma SH-SY5Y cells and mouse primary hippocampal neurons were transfected with the IVT mRNA and antibody translation and ability to bind tau was assessed. RESULT: Transfection of mammalian cells with IVT synthesised mRNA results in the translation of a secreted tau-specific IgG and an intracellular scFv intrabody. Importantly, both antibody formats engage tau, with the intrabody engaging tau directly within the cell cytoplasm. CONCLUSION: IVT synthesised mRNA can be used to generate both functional full-length IgG antibodies and scFv intrabodies targeting tau. Our study highlights the utility of mRNA as an inexpensive and versatile delivery platform for antibody therapeutics.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.087103