Over 100,000 human diseases are caused by genetic alterations in the genome, and only a very small portion of these diseases can be cured. Gene editing represents a pivotal development in disease therapeutics as a powerful tool to correct defects and mutations within the genome. In particular, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas9 represents a paradigm shift in the ability to make precise, targeted genomic change. Recently, a few approaches have been developed for intracellular delivery of CRISPR/Cas9 complexes. While these approaches have some degree of success, it remains extremely challenging to achieve highly effective and efficient intracellular CRISPR/Cas9 delivery. This EArly-concept Grants for Exploratory Research (EAGER) grant supports research to design, manufacture, and test nanobots or nanoscale robots that can precisely target and deliver CRISPR/Cas9 to diseased cells and release the gene-editing agencies in a controlled fashion. The three-dimensional nanoscale printing method for fabricating the nanobots involves multi-materials printing and could be a powerful tool for scalable nanomanufacturing of functional nanoscale machines for a variety of applications. The nanobots could revolutionize gene or drug delivery to repair genetic disorder of many human diseases, which would have a strong impact on human health. The project offers exciting interdisciplinary training that integrates content from manufacturing to biomaterials to nanomachines to therapeutics for a diverse group of graduate and undergraduate students. Nanoscale printing and nanobots are excellent tools for laboratory demonstrations to attract high school students and teachers, and women and underrepresented minority researchers to science and engineering fields.

This project aims to investigate the nanomanufacturing processing of a novel nanobot system for targeted gene or drug delivery at the single cell level. The collaborative research team designs the nanobot using biocompatible materials and uses a nanoscale 3D printing system to fabricate it. The nanobot consists of a magnetic nanomotor and a biodegradable nano-cargo. The nanomotor, which is typically 200 nm round and 400 nm long, is 3D printed by embedding iron oxide magnetic nanoparticles in hydrogel. The nano-cargo, which is of similar dimensions, is also 3D printed by encapsulating CRISPR/Cas9 in a biodegradable hydrogel, so that CRISPR/Cas9 can be released through biodegradation once inside the cell. Fundamental research focuses on investigating the effects of material composition and properties, and nanomanufacturing processing parameters on the nanobot performance. The team also tests the efficacy of the nanobot to deliver CRISPR/Cas9 into cancer cells for tumor suppression. The scalability of the nanomanufacturing process is demonstrated through the reproducible fabrication of an array of nanobots.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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University of California San Diego
La Jolla
United States
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