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As gene- and stem cell-based therapies emerge as viable medical interventions across a variety of disease entities, the need for rapid, safe, cost effective, and efficient gene delivery and editing technologies represents a significant hurdle to broader clinical translation. While existing viralvector-based and non-viral gene-transfer methods are used routinely in laboratory settings, thesestrategies are problematic when scaled up for clinically relevant applications targeting the manufacture of therapeutic cell products. Developing approaches that can simultaneously satisfy universal cargo delivery, high efficiency, high throughput, minimal cell toxicity, and scalability remains a long-term challenge. My current research explores the ultimate limits of miniaturization to target nanoscience-inspired solutions to this challenge. By leveraging advances in bioengineering, materials science, and molecular biology, including microfluidics, nanofabrication, and gene editing approaches, we develop and apply techniques where cells are manipulated using either sharp nanostructures or via physical means to induce transient membrane disruption. In one example, we accomplish this task via the design of technologies that use acoustic waves generated within microfluidic systems (i.e., acoustofluidics). In this approach, oscillations from piezoelectric transducers mounted onto glass microcapillaries are used to generate standing bulk acoustic waves (BAWs) within the microfluidic network. As cells are rapidly passed through pressure nodes established by acoustic radiation forces generated by the BAW field, they experience sheer forces that stretch their membranes and establish small areas of phase separation. These biophysical interactions effectively render the plasma and nuclear membranes of targeted cells temporarily porous for approximately 5-10 min, facilitating rapid and efficient entry of biomolecular cargo intracellularly. These cargoes (e.g., DNA, microRNAs, CRISPR/Cas9 gene editing machinery) may be delivered directly or packaged into nanoparticle-based carriers. These capabilities ultimately empower our efforts to create tools that enable stem cell biologists to probe and to interact with stem cells more precisely and empower clinical scientists to apply this knowledge to design and implement new therapies more rapidly and broadly.
A selected list of publications:
Published in Proceedings of the National Academy of Sciences on Tuesday May 19, 2020.
Published in Advanced Science on Thursday April 16, 2020.
Published in Applied Materials & Interfaces on Monday February 24, 2020.
Published in Proceedings of the National Academy of Sciences on Tuesday December 3, 2019.
Published in Applied Materials & Interfaces on Wednesday March 20, 2019.
Published in ACS Nano on Wednesday March 14, 2018.
Published in ACS Chemical Neuroscience on Monday December 4, 2017.
Published in ACS Nano on Thursday September 28, 2017.
Published in Proceedings of the National Academy of Sciences on Friday September 12, 2008.