siRNA is a part of an innovative strategy to disrupt the activity of cancer-related genes that has broad applications to other diseases.
In the May 1 issue of Cancer Research, the scientists reported that a multistage nanovector system for the delivery of siRNA significantly lengthened the therapeutic effects of the treatment in two independent mouse models of advanced ovarian cancer.
The researchers reported that a single intravenous dose of siRNA targeting the EphA2 oncoprotein provided the same tumor shrinkage for three weeks as that now achieved by six doses over the same period.
“The multistage delivery system is revolutionary in that it allows the therapeutic payloads to cross the biological barriers in the body and reach their target. It further helps release agents over long periods of time directly into the bloodstream, which is unprecedented,” said Mauro Ferrari, Ph.D., chairman of the Department of NanoMedicine and Biomedical Engineering at The University of Texas Medical School at Houston, which is part of UTHealth. “We are very excited about the results of this paper, since it provides the first validation of the therapeutic advantages of the multistage delivery system in animal models of cancer.”
The multistage nanovector system is composed of nanoporous silicon carrier particles that are about 100 times smaller than a strand of hair, which can be loaded with tiny bubbles of fat called nanoliposomes containing siRNA. The system provides for the release of the nanoliposomes and their contents.
“This is an exciting development because RNA interference has worked well in an animal model but has such a short half-life that it requires frequent delivery. A three-week dosing period is much closer to the sustained dosing needed to properly test this therapy in clinical trials,” said Anil Sood, M.D., professor in M.D. Anderson’s Departments of Gynecological Oncology and Cancer Biology.
The multistage nanovector system was developed in Ferrari’s laboratory and the liposomal siRNA was developed at M. D. Anderson.
“We have provided the first in vivo therapeutic validation of a novel, multistage siRNA delivery system for sustained gene silencing with broad applicability to pathologies,” wrote Takemi Tanaka, Ph.D., a co-first author and a research assistant professor of nanomedicine and biomedical engineering at the UT Medical School at Houston, and the other investigators in the paper..
Gabriel Lopez-Berestein, M.D., professor of experimental therapeutics at M. D. Anderson, Sood, co-director of M. D. Anderson’s Center for RNA Interference and Non-Coding RNA, and Ferrari are the senior authors.
“EphA2 is an important target because it’s overexpressed in 70 percent of ovarian cancers and is strongly associated with poor survival and a higher likelihood of advanced or metastatic disease,” said Lopez-Berestein. “It’s also overexpressed in melanoma, breast and lung cancers with the same poor prospects for patients.”
The protein is not present in normal tissue and cannot be attacked using more traditional drug approaches.
Study contributors from UTHealth include: René Nieves-Alicea, Ph.D.; Aman Preet Singh Mann, Xuewu Liu, Ph.D.; Rohan Bhavane, Jianhua Gu, Jean Fakhoury and Biana Godin, Ph.D.
M. D. Anderson contributors include: Lingegowda S. Mangala, Ph.D., co-first author; Edna Mora, M.D.; Hee-Dong Han, Pablo E. Vivas-Mejia, Ph.D.; Mian M.K. Shahzad, Chunhua Lu, Koji Matsuo, Rebecca Stone, M.D.; and Alpa Nick, M.D.
Ciro Chiappini, a graduate research assistant at The University of Texas at Austin, also contributed to the study.
The study, which is titled “Sustained Small Interfering RNA Delivery by Mesoporous Silicon Particles,” received support from the Department of Defense, the State of Texas Emerging Technology Fund, National Aeronautics and Space Administration, the Ovarian Cancer Research Fund Program Project Development Grant, The University of Texas M.D. Anderson Cancer Center Ovarian Cancer Specialized Program of Research Excellence, the National Institutes of Health, the Zarrow Foundation, the Betty Ann Asche Murray Distinguished Professorship, the Baylor WRHR Grant and the GCF Molly-Cade Ovarian Cancer Research Grant and the Alliance for NanoHealth.
Ferrari serves as a professor of experimental therapeutics at the M. D. Anderson Cancer Center, adjunct professor of bioengineering at Rice University, adjunct professor of biochemistry and molecular biology at The University of Texas Medical Branch at Galveston, adjunct professor of engineering at the University of Houston, and president of the Alliance for NanoHealth.Rob Cahill
Robert Cahill | EurekAlert!
Tag it EASI – a new method for accurate protein analysis
20.06.2018 | Max-Planck-Institut für Biochemie
How to track and trace a protein: Nanosensors monitor intracellular deliveries
19.06.2018 | Universität Basel
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
20.06.2018 | Materials Sciences
20.06.2018 | Materials Sciences
20.06.2018 | Materials Sciences