Steven Jonas

Steven Jonas, Ph.D.

Office Address:
A2-410 MDCC


Assistant Professor,Pediatrics
Research Interests

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:

Acoustofluidic sonoporation for gene delivery to human hematopoietic stem and progenitor cells
Published in Proceedings of the National Academy of Sciences on Tuesday May 19, 2020.
Dual Supramolecular Nanoparticle Vectors Enable CRISPR/Cas9-Mediated Knockin of Retinoschisin 1 Gene—A Potential Nonviral Therapeutic Solution for X-Linked Juvenile Retinoschisis
Published in Advanced Science on Thursday April 16, 2020.
Lipid Bicelle Micropatterning Using Chemical Lift-Off Lithography
Published in Applied Materials & Interfaces on Monday February 24, 2020.
An Absence of Lamin B1 in Migrating Neurons Causes Nuclear Membrane Ruptures and Cell Death
Published in Proceedings of the National Academy of Sciences on Tuesday December 3, 2019.
Bio-Inspired NanoVilli Chips for Enhanced Capture of Tumor-Derived Extracellular Vesicles: Toward Non-Invasive Detection of Gene Alterations in Non-Small Cell Lung Cancer
Published in Applied Materials & Interfaces on Wednesday March 20, 2019.
Precision-Guided Nanospears for Targeted and High-Throughput Intracellular Gene Delivery
Published in ACS Nano on Wednesday March 14, 2018.
Precision Medicine in Pediatric Neurooncology: A Review
Published in ACS Chemical Neuroscience on Monday December 4, 2017.
Multiple-Patterning Nanosphere Lithography for Fabricating Periodic Three-Dimensional Hierarchical Nanostructures
Published in ACS Nano on Thursday September 28, 2017.
Hydrophobic Surfaces for Enhanced Differentiation of Embryonic Stem Cell-Derived Embryoid Bodies
Published in Proceedings of the National Academy of Sciences on Friday September 12, 2008.