Wongsodirdjo, P.; Caruso, A. C.; Yong, A.; Lester, M.; Vella, L. J.; Hung, Y. H.; Nisbet, R. M.

Monoclonal antibodies (mAbs) have emerged as a leading therapeutic agent for the treatment of disease, including Alzheimer\'s disease. In the last year, two anti-amyloid mAbs, lecanemab and aducanumab, have been approved in the USA for the treatment of Alzheimer\'s disease (AD). There are currently several Tau-targeting mAbs in clinical development also for the treatment of AD. MAbs, however, are expensive and timely to produce and require frequent dosing. Synthetic in vitro transcribed (IVT) mRNA for endogenous protein expression may overcome many of the limitations of protein antibody production and has recently been utilized for antibody delivery. Here we generated synthetic IVT mRNA encoding a Tau specific monoclonal antibody as a full-length IgG and as a single chain variable fragment (scFv). We have demonstrated the ability of the IVT mRNA to be translated into functional Tau-specific antibodies. Furthermore, we demonstrate the ability of the Tau-specific scFv to specifically engage intracellular Tau. This work highlights the utility of mRNA for the delivery of antibody therapeutics, including intrabodies, for the targeting of Tau in tauopathies.