MOLECULAR REBAR DESIGN LLC — Department of Defense SBIR Phase II: DHA211-010

Description

DNA encoded monoclonal antibodies (dmAbs) have been shown to be an effective treatment against a range of infectious diseases including Ebola, Zika, and HIV.  However, delivering plasmid DNA into cells and tissues safely and effectively is a challenge that has so far prevented widespread adoption of dmAbs as a therapeutic.  In Phase I of this project, Molecular Rebar Design (MRD) introduced a solution to the problem of dmAb transport in the form of Medical Grade Molecular Rebar (MGMR), a discrete, multiwalled carbon nanotube based biomolecular delivery platform.  We demonstrated that MGMR can be efficiently loaded and unloaded with dmAbs, can be used to transiently and stably transfect CHO-K1 cells, and can do so while maintaining high cellular viability.  In Phase II we aim to continue the project by refining MGMR for both in vitro and in vivo systems.  First, we will produce a plasmid vector encoded with HIV specific monoclonal antibodies from the incomplete plasmid construct tested in Phase I.  We will demonstrate that this complete plasmid can be loaded, offloaded, and remains well dispersed when complexed with MGMR in physiological solution.  Furthermore, we will build upon the successful transfection of CHO-K1 cells demonstrated in Phase I and optimize MGMR mediated transient and stable transfection resulting in the production of high levels of HIV specific monoclonal antibodies in vitro. The second half of the proposed project will expand MGMR’s utility as a DNA encoded monoclonal antibody delivery device to in vivo systems.  MRD has partnered with Professor Lin Zhu at the Texas A&M College of Pharmacy to develop a series of dmAb loaded MGMR studies optimizing the delivery system for small animals, specifically BALB/c mice.  Several dosing volumes, routes of administration, and MGMR formulations will be tested in order to produce the maximum number of HIV specific monoclonal antibodies in serum while maintaining mice health.  The ideal treatment conditions learned in these experiments will be essential for the final portion of Phase II: a large animal study of dmAb loaded onto MGMR for HIV treatment.  MRD has planned an experiment with the Texas Biomedical Research Institute using rhesus macaques as a large animal model, and we expect to administer loaded MGMR that produces high levels of HIV antibodies in serum while preserving animal health.