CAREER: Photoactivated miRNA delivery for modulation of human adipose stromal cell differentiation

1254281

Hayes

Modulation of cell and tissue function with microRNA (miRNA), which are small non-coding RNA sequences naturally found in animal and plant tissues, is a promising technique to improve the control of wound healing and tissue repair processes. When combined with adult stem/stromal cell (ASC) therapies these techniques may result in a new regenerative medicine paradigm. Several miRNA and other potential oligonucleotide based therapeutics have been demonstrated to posses potent bioactivity but current state-of-the-art oligonucleotide delivery techniques are largely incompatible with clinical therapies due to toxicity and lack of specific action. This project will address the critical need for a clinically relevant, safe and effective miRNA delivery system which provides temporal and spatial control of activation at the site of diseased or damaged tissue. As a primary objective the project will optimize, a nanoparticle (NP) based, light activated, miRNA delivery system (LAMD) for the light activated spatial and temporal regulation of bone and blood vessel formation using ASC as a model system. A secondary objective is the development of a more cost effective and robust processes for the fabrication of a targeted version of the basic LAMD system. Research into manufacturing processes with improved yields and morphological control will address a critical limitation to the development of therapies using targeted particles.

With the lengthening life span and increasing activity levels of the aging population we expect to see a substantial increase in the number of patients presenting with orthopaedic injuries. Of particular interest are solutions to skeletal disorders, such as bone disunions and non-healing, critical sized defects caused by wear, cancers, trauma or as the result joint replacement. The development of a photoactivated, nanoparticle based, miRNA delivery system that addresses the limitations of traditional miRNA delivery vectors while providing for spatial and temporal control of activity could be transformative for miRNA use in regenerative medicine. This project will provide direct support for several undergraduate and graduate students per year to work on this project as research scholars. The project presents a unique and interdisciplinary opportunity for students majoring in biomedical engineering, chemistry and related fields to build fundamental knowledge and appreciation in the areas of nanomaterial synthesis, stem cell biology, photobiology and regenerative medicine. The outreach components of this project will include K-12, undergraduate and graduate education activities.