We have anti-arthritis drugs. What we lack is the ability to deploy them when and where they are needed in the body. The drugs would be far more effective, and occasion fewer side effects, if they were to appear only in response to inflammation, and only in the joints. If the drugs could be delivered so painstakingly—so smartly—they wouldn’t have to be administered systemically.
Although conventional drug delivery systems may be unable to respond to arthritic flares with such adroitness, cells may have better luck—if they are suitably modified. Stem cells, for example, have been “rewired” by means of gene-editing technology to fight arthritis. These stem cells, known as SMART cells (Stem cells Modified for Autonomous Regenerative Therapy), develop into cartilage cells that produce a biologic anti-inflammatory drug. Ideally, the new cartilage cells will replace arthritic cartilage, and the biologic will protect against chronic inflammation, preserving joints and other tissues.
SMART cells of this sort were prepared by scientists based at Washington University School of Medicine in St. Louis. The scientists initially worked with skin cells taken from the tails of mice and converted those cells into stem cells. Then, using the gene-editing tool CRISPR in cells grown in culture, they removed a key gene in the inflammatory process and replaced it with a gene that releases a biologic drug that combats inflammation.
Details of this work appeared April 27 in the journal Stem Cell Reports, in an article entitled “Genome Engineering of Stem Cells for Autonomously Regulated, Closed-Loop Delivery of Biologic Drugs.” The article describes how modified stem cells grew into cartilage and produced cartilage tissue. The engineered cartilage, the scientists reported, was protected from inflammation.
“Using the CRISPR/Cas9 genome-engineering system, we created stem cells that antagonize IL-1- [interleukin-1] or TNF-α- [tumor necrosis factor-α] mediated inflammation in an autoregulated, feedback-controlled manner,” wrote the authors of the Stem Cell Reports article. “Our results show that genome engineering can be used successfully to rewire endogenous cell circuits to allow for prescribed input/output relationships between inflammatory mediators and their antagonists, providing a foundation for cell-based drug delivery or cell-based vaccines via a rapidly responsive, autoregulated system.”
Many current drugs used to treat arthritis—including Enbrel® (etanercept), Humira® (adalimumab), and Remicade® (infliximab)—attack TNF-α, an inflammation-promoting molecule. But the problem with these drugs is that they are given systemically rather than targeted to joints. As a result, they interfere with the immune system throughout the body and can make patients susceptible to side effects such…