Category: High-Definition Biotechnology

1140-A - Topical Nucleic Acid Nanotechnology for Molecular Diagnosis of Skin Diseases

Monday, February 5, 2018
2:00 PM - 3:00 PM

The gold standard for skin disease diagnosis typically requires tissue extraction (biopsy), followed by sample processing, staining and imaging to identify biomarkers of interest through histopathology. Skin biopsies are painful, inconvenient (often requiring suture removal later), risk infection, and typically leave a scar. In addition, performing pathologic assessment is labour-intensive and time-consuming (taking a week or more), limiting the clinician’s rapid decision-making and initiation of treatment. Gene-profiling and spectroscopic methods attempt to address these unmet needs, although they have limited precision and diagnostic value.

Spherical nucleic acids (SNA) have emerged as potent topical agents that penetrate human skin and cause epidermal and dermal gene target knockdown. NanoFlares, are SNA constructs that generate a nucleic acid sequence-specific fluorescent response when they hybridize with intracellular mRNA targets, useful for measuring live cell mRNA levels. To date, they have not been explored as in vivo diagnostic tools. Herein, NanoFlares are topically applied to measure connective tissue growth factor (CTGF) expression as a visual indicator of pathological (hypertrophic, keloid) scarring. In vitro NanoFlares exhibit sufficiently high resolution to distinguish diseased fibroblasts from normal cells, including any regulatory effect of transforming growth factor (TGF)-β agonists and antagonists.

To evaluate clinical feasibility, NanoFlares were applied topically to live mice, rabbits, as well as ex vivo human skin disease models. Transepidermal penetration was ascertained, as well as the spectroscopic identification and quantification of diseased fibroblasts from their CTGF mRNA expression. These studies provide proof-of-concept for the clinical use of topically applied NanoFlare technology for making point-of-care diagnostic decisions based on the mRNA expression profile of skin disorders while significantly reducing healthcare burden.

David Yeo

Post-doctoral Research Fellow
Nanyang Technological University
Singapore, Singapore

David Yeo, PhD is a Research Fellow at the School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore. He holds Master's and Doctoral degrees from Imperial College London, UK in Materials Science and Chemical Engineering respectively. He is passionate about applying multi-disciplinary Engineering to solve problems for biomedicine. In particular, he has scaled-up bioprocesses to facilitate stem cell therapy and developed process-enabling technology (e.g. nano-diagnostics, therapeutics, cell separation) for stem cells, cancer and dermatology. These have been highlighted in various SMART and NMRC grants (Singapore). He constantly seeks to validate these technologies through collaboration and translation with clinically-relevant disease models.
David has also lectured and tutored 6 undergraduate modules and personally mentored 10 students. To date, he has published 22 peer-reviewed articles, 1 book chapter and received 11 prizes for scientific and communication proficiency. Beyond academia, his interests lie in Biomedical innovation, public engagement and he serves as a section editor for the society for laboratory automation and screening (SLAS) Technology journal.

-Biomedical Engineer with a focus on Nanomedicine.
-Specifically: nucleic acid diagnostics/therapeutics for skin disease and other epithelial disorders.
-Current Goal: develop Point-of-Care thera-nostics using nucleic acid nanotechnology.