 |
Mohammad Aghaamoo, PhD Biomedical Engineering Mentor: Dr. Abraham Lee |
|
Abstract |
|
In recent years, cell reprogramming and gene editing have had tremendous impacts on gene and cell-based therapies, biomanufacturing, and basic research (e.g., cell biology, drug discovery, and genetics). Macrophages and dendritic cells (DCs) are among promising candidates for cell reprogramming. Due to their functional diversity, the ability to genetically modify and reprogram macrophages and DCs not only can significantly contribute to better understand their fundamental biology and associated diseases, but also provides opportunities to develop effective therapeutics. However, a key challenge in engineering macrophages and DCs is that these cells are notoriously difficult-to- transfect. Throughout my Ph.D. studies under supervision of Dr. Abraham Lee at UC Irvine, I developed an Acoustic-Electrical Shear Orbiting Poration (AESOP) platform for non-viral intracellular delivery of a wide range of cargos with high efficiency, uniformity, cell viability, and throughput of 1 million cells/min per single chip. As for my ICTS training and under the mentorship of Dr. Abraham Lee and Dr. Wendy Liu, I plan to adopt and develop the AESOP technology to specifically address the challenges in engineering macrophages and DCs. The goal is to rival viral transduction, electroporation, and other non-viral technologies by achieving high delivery efficiency while maintaining cell viability and functionality, dosage-controlled delivery of cargos, and high-throughput cell processing. My specific aims are: (1) Optimize the delivery of intended cargo sizes into macrophages and DCs with uniform poration of the cell membranes via mechanical shear followed by the modulated expansion of these nanopores via electric field, (2) Demonstrate AESOP for gene editing and cell reprogramming of macrophages and DCs while preserving their functionality, and (3) Design prototype of AESOP instrumentation and quantitative benchmark of AESOP with both viral and nonviral transfection techniques. |
