Title: Next-generation CRISPR/Cas for targeting DNA and RNA
Abstract: CRISPR technologies have transformed modern biology, medicine, and biotechnology, yet most platforms remain constrained by reliance on RNA guides that are costly, unstable, and prone to off-target activity, particularly in RNA-targeting applications. Over the past decade, our laboratory has developed a broad portfolio of CRISPR-based technologies for genome editing and molecular diagnostics, including modular delivery systems, programmable nucleic acid sensors, machine-learning-guided enzyme engineering strategies, and precision genome rewriting tools. In this seminar, I will highlight some of these platforms and their applications in research and translational settings, spanning viral and cancer diagnostics, genome modification, and therapeutic development. Building on this foundation, I will introduce a first-in-class DNA-guided CRISPR/Cas12 platform enabled by “pseudo-guide DNA” (ΨDNA), which programs type V Cas12 enzymes for precise RNA recognition and regulation without collateral RNA degradation. Through integrated biochemical and cellular analyses, we establish the mechanistic basis of ΨDNA-mediated targeting, including kinetic profiling and high-throughput guide screening. Transcriptome-wide profiling reveals sequence-specific RNA engagement and a ribosome-stalling associated decay mechanism with minimal off-target effects. We demonstrate efficient multiplexed transcript knockdown, sensitive RNA detection, programmable epitranscriptomic modification, and dual DNA and RNA editing within a single effector system. Collectively, this work highlights a unified strategy for building scalable, high-fidelity CRISPR technologies and new opportunities in diagnostics, synthetic biology, and therapeutic translation.
Bio: Piyush K. Jain is an Exxon Mobil Gator Alumni Faculty Endowed Professor and Associate Professor in the Department of Chemical Engineering at the University of Florida and a Senior Member of the National Academy of Inventors (NAI). His research focuses on developing next-generation CRISPR-based diagnostics and genome-editing technologies at the intersection of biomolecular engineering and synthetic biology. Dr. Jain received his bachelor’s degree in pharmacy in India and completed his Ph.D. at the University of Missouri-Kansas City under the supervision of Prof. Simon Friedman, where he pioneered light-responsive biochemical tools. He subsequently conducted postdoctoral research at the Massachusetts Institute of Technology in Prof. Sangeeta Bhatia’s laboratory, developing light-responsive nanosensors and gene-editing technologies. Dr. Jain’s work is widely published in high-impact journals and has been highlighted by over 10,000 media outlets worldwide, including a TEDx talk. He holds over 40 issued or pending patents, has licensed technologies from MIT, and has co-founded multiple startups, including CasNx, focused on translating CRISPR-based technologies for diagnostics and therapeutics. His research has been supported by 18 grants from agencies including the NIH, NSF, CDC, USDA, and industry totaling up to $23 million, and he has received honors including the Shah Rising Star Professorship, the UF Provost Excellence Award, and the NIH MIRA-ESI (R35) award.
10:30am, Remsen Hall 1