Incorporation of ChatGPT and Other Large Language Models into a Graduate Level Computational Bioengineering Course.

The remarkable capabilities of generative artificial intelligence and large language models (LLMs) such as ChatGPT have delighted users around the world. Educators have regarded these tools as either a cause for great concern, an opportunity to educate students on cutting-edge technology, or often some combination of the two. Throughout the Fall 2023 semester, we explored the use of ChatGPT (and Bard, among other LLMs) in a graduate level numerical and statistical methods course for PhD-level bioengineers. In this article we share examples of this ChatGPT content, our observations on what worked best in our course, and speculate on how bioengineering students may be best served by this technology in the future.

Designing Synthetic Polymers for Nucleic Acid Complexation and Delivery: From Polyplexes to Micelleplexes to Triggered Degradation.

Gene delivery as a therapeutic tool continues to advance toward impacting human health, with several gene therapy products receiving FDA approval over the past 5 years. Despite this important progress, the safety and efficacy of gene therapy methodology requires further improvement to ensure that nucleic acid therapeutics reach the desired targets while minimizing adverse effects. Synthetic polymers offer several enticing features as nucleic acid delivery vectors due to their versatile functionalities and architectures and the ability of synthetic chemists to rapidly build large libraries of polymeric candidates equipped for DNA/RNA complexation and transport. Current synthetic designs are pursuing challenging objectives that seek to improve transfection efficiency and, at the same time, mitigate cytotoxicity. This Perspective will describe recent work in polymer-based gene complexation and delivery vectors in which cationic polyelectrolytes are modified synthetically by introduction of additional components─including hydrophobic, hydrophilic, and fluorinated units─as well as embedding of degradable linkages within the macromolecular structure. As will be seen, recent advances employing these emerging design strategies are promising with respect to their excellent biocompatibility and transfection capability, suggesting continued promise of synthetic polymer gene delivery vectors going forward.

Enhancing Prednisone-Based Arthritis Therapy with Targeted IL-27 Gene Delivery.

Rheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized primarily by synovial hyperplasia and accumulation of several types of immune infiltrates that promote progressive destruction of the articular structure. Glucocorticoids are often prescribed to treat RA because of their strong anti-inflammatory and immunosuppressive effects. However, their application must be limited to the short-term due to a risk of adverse events. In the present study, we examined the potential combination of low-dose prednisone with gene delivery of an agent of promising and complementary effectiveness in RA, interleukin (IL)-27. IL-27 has been shown to have anti-inflammatory potential, while also acting as an effective bone-normalization agent in prior reports. The present report examined a version of IL-27 targeted at the C-terminus with a short 'peptide L' (pepL, LSLITRL) that binds the interleukin 6 receptor α (IL-6Rα) upregulated during inflammation. By focusing on this targeted form, IL-27pepL or 27pL, we examined whether the anti-inflammatory potential of prednisone (at a relatively low dose and short duration) could be further enhanced in the presence of 27pL as a therapy adjuvant. Our results indicate that 27pL represents a novel tool for use as an adjuvant with current therapeutics, such as prednisone, against inflammatory conditions.

Sonodelivery in Skeletal Muscle: Current Approaches and Future Potential.

There are currently multiple approaches to facilitate gene therapy via intramuscular gene delivery, such as electroporation, viral delivery, or direct DNA injection with or without polymeric carriers. Each of these methods has benefits, but each method also has shortcomings preventing it from being established as the ideal technique. A promising method, ultrasound-mediated gene delivery (or sonodelivery) is inexpensive, widely available, reusable, minimally invasive, and safe. Hurdles to utilizing sonodelivery include choosing from a large variety of conditions, which are often dependent on the equipment and/or research group, and moderate transfection efficiencies when compared to some other gene delivery methods. In this review, we provide a comprehensive look at the breadth of sonodelivery techniques for intramuscular gene delivery and suggest future directions for this continuously evolving field.