# Rapid In Vivo Screening of Monoclonal Antibody Cocktails Using Hydrodynamic Delivery of DNA-Encoded Modified Antibodies

## TL;DR

This study introduces a fast and cost-effective method to test monoclonal antibody treatments in mice using DNA delivery, speeding up the development of therapies for infectious diseases.

## Contribution

A novel method for rapid in vivo screening of monoclonal antibody cocktails using DNA-encoded modified antibodies and hydrodynamic delivery.

## Key findings

- The method enabled high expression of scFv-IgG in mice.
- The approach provided protection in two murine infection models.
- It allows for rapid and low-cost screening of therapeutic mAb candidates.

## Abstract

Background: Monoclonal antibodies (mAbs) are potent treatment options for infectious diseases. The rapid isolation and in vivo validation of therapeutic mAb candidates, including mAb cocktails, are essential to combat novel or rapidly mutating pathogens. The rapid selection and production of mAb candidates in sufficient amount and quality for preclinical studies are a major limiting step in the mAb development pipeline. Methods: Here, we developed a method to facilitate the screening of therapeutic mAbs in mouse models. Four conventional mAbs were transformed into single-chain variable fragments fused to the fragment crystallizable (Fc) region of a human IgG1 (scFv-IgG). These scFv-IgG were expressed individually or as a cocktail in vitro and in mice following transfection or hydrodynamic delivery of the corresponding plasmids. Results: This method induced high expression of all scFv-IgG and provided protection in two murine infection models. Conclusions: This study highlights the benefits of this approach for the rapid, low-cost screening of therapeutic mAb candidates.