BME Seminar Series Laura Ensign-Hodges, PhD, Johns Hopkins Medicine

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Headshot of Ensign-Hodges

Larua Ensign-Hodges, PhD

Marcella E. Woll Professor of Ophthalmology
Vice Chair for Research
Wilmer Eye Institute
Johns Hopkins School of Medicine
 

Title: "Machine Learning-driven Peptide Engineering for Sustained Ocular Drug Delivery"

 

Abstract

Sustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to

impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye. We develop a super learning-based methodology to engineer multifunctional peptides that efficiently enter cells, bind to melanin, and have low cytotoxicity. When the lead multifunctional peptide (HR97) was conjugated to an intraocular pressure lowering drug that is prescribed for three times per day topical dosing, intraocular pressure reduction was observed for up to 18 days after a single intracameral injection in rabbits. When HR97 was conjugated to a neuroprotective drug, topical administration led to therapeutic delivery to the posterior segment to protect retinal ganglion cells in rats up to 2 weeks after the last eye drop dose. Importantly, therapeutically relevant drug concentrations were achieved with topical dosing in rabbits. Engineered multifunctional peptide-drug conjugates are a promising approach for providing sustained therapeutic delivery in the eye and beyond.

 

Bio

Laura M. Ensign, Ph.D., is the Marcella E. Woll Professor of Ophthalmology and the Vice Chair for Research in the Wilmer Eye Institute at the Johns Hopkins University School of Medicine. She has secondary appointments in Chemical & Biomolecular Engineering, Biomedical Engineering, Pharmacology and Molecular Sciences, Gynecology & Obstetrics, Infectious Diseases, and Oncology. Dr. Ensign’s research focuses on the principle of characterizing biological barriers in health and disease in order to design more efficacious formulations for prophylactic and therapeutic drug delivery, and has already led to the translation of pharmaceutical products that improve clinical management of human disease. She is an inventor on numerous patents licensed to pharmaceutical companies, including many protecting FDA-approved therapies, and she has co-founded three start-up companies at various stages of clinical trials. Here, Dr. Ensign will describe the application of machine learning to engineer peptides as functional adapters that prolong the therapeutic duration of drugs in the eye.

Category: Seminar Series