The Whitehead Lab has two major thrusts in the area of drug delivery:
1. RNA delivery and genetic engineering. Nucleic acid drugs, including DNA and many types of RNA, are the medicines of the future, and they will enable personalized therapies that will revolutionize our ability to treat disease. Unfortunately, if you administer these drugs in "naked" form, they are rapidly degraded in the body. Therefore, before these drugs can be FDA approved, we need to develop delivery systems able to package up this sensitive nucleic acid cargo and escort it to the right cells and organ targets in the body. Using our lipid nanoparticle technology, our lab asks questions related to the effect of lipid chemistry on efficacy, toxicity, and immune response. Ultimately, we are interested in using our lipid nanoparticle RNA delivery vehicles to prevent disease through vaccinations and treat diseases that range from Type I diabetes to inflammatory bowel disease.
2. Oral delivery of macromolecules. Currently, the only means of administering proteins (e.g. insulin) and other macromolecular drugs is by injection, which is painful and prone to patient non-compliance. Half of our lab focuses on developing the technology needed to deliver protein, peptide, and nucleic acid drugs orally. This is challenging because our gastrointestinal tract is designed to break down these compounds, not absorb them intact. Our lab engineers permeation enhancers, natural products, and polymer-protein sytems to enable safe delivery of protein drugs for therapeutic effect.
Our interests evolve continually, and the projects listed below are only a partial representation of the exciting work currently being conducted in our lab.
Although oral delivery is the most patient-friendly route of drug administration, it cannot be utilized for macromolecules because of their susceptibility to enzymatic degradation in the GI tract and low permeability across the intestinal epithelium. We seek to understand the effect of tight junction and epithelial membrane proteins on drug transport and permeation enhancement processes - with a goal of applying this understanding to both the oral delivery of systemic drugs and treatment of inflammatory bowel disease. Click here for a video describing some of our oral delivery work.
Each year, non-Hodgkin B-cell lymphoma kills over 20,000 people in the U.S., and a strong need remains for the development of novel therapies capable of eradicating solid and disseminated B-cell lymphomas. We are interested in the role of non-adherent membrane proteins on cell uptake and the development of targeted siRNA nanoparticles capable of selectively entering and destroying lymphoma cells.
Chronic wounds pose a significant and growing biomedical burden, afflicting ~6.5 million people and costing over $25 billion annually in the U.S. Using RNA interference, we seek to better understand five molecular contributors to chronic wound development and persistance. Our utlimate goal is to engineer a therapeutic polymer ointment loaded with nanoparticles and drugs that will address the underlying causes of chronic wound pathophysiology.
The chemical structure of the various agents comprising drug delivery systems can have a tremendous influence on the delivery process. We are interested in characterizing the effects of specialized classes of small molecules, lipids, and polymers on permeabilization, transfection, and immune responses.
Oral Delivery of Biologic Drugs
Mantle Cell Lymphoma Nanoparticle Therapy
Diabetic Wound Healing
Influence of Chemical Structure on the Biological Response to Nanomaterials