A team of Johns Hopkins researchers discovered that adjusting the thickness of cell culture media — the fluids cells inhabit in a laboratory environment—to match human body fluids could boost gene therapy effectiveness and affordability. Their research, “Tuning extracellular fluid viscosity to enhance transfection efficiency” appears in Nature Chemical Engineering.
Gene therapies are promising treatments for many acquired and congenital diseases, but their development is costly due to transfection, the process by which nucleic acids (DNA and RNA) are inserted into cells to alter gene expression or produce specific proteins. Carriers like nanoparticles or synthetic viruses deliver these nucleic acids to the body, inducing biological responses in targeted cells.
While there have been advancements to the transfection process, it is still inefficient and expensive. In an effort to improve the process to make gene therapies accessible to more patients, Hai-Quan Mao, director of the Institute for NanoBioTechnology and professor of materials science and engineering, and his team studied an overlooked biophysical property that offers promising results: viscosity.
“Most cell culture media used in transfection are about the consistency of water. By adjusting the viscosity to resemble that of blood and interstitial fluid, we substantially improved transfection efficiency,” said Mao.
Led by materials science and engineering PhD student Jingyao Ma and biomedical engineering PhD student Yining Zhu, the team systematically adjusted cell culture media viscosity and tested its effect on transfection of various cell types and carriers, including fat-based nanoparticles, complexes made of polymers and DNA (polyplexes), and two types of virus-based carriers (adeno-associated vectors and lentiviral vectors).
“Each carrier showed a ‘Goldilocks zone where maximum transfection occurred depending on the media viscosity. Overall, transfection improved two- to 60-fold across all the carriers tested when the media resembled the viscosity of bodily fluids,” Ma said.
The researchers say their results have broad applications. For instance, their approach could be integrated into existing gene and cell therapy manufacturing processes to produce more treatments with the same resources. By lowering production costs and increasing yield, manufacturers could offer more affordable treatments to patients. They also suggest that their research could make preclinical studies more accurate, helping to accelerate the development and approval of new gene therapies.
“This research has the potential to transform the landscape of gene therapy by making it more efficient, scalable, and accessible to a broader population,” said Zhu.
Original article link: “https://engineering.jhu.edu/news/goldilocks-breakthrough-in-gene-therapy-development/“
