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Ready to run with shRNA
WALTHAM, Mass.—Thermo Fisher Scientific Inc. has, in collaboration with Baltimore-based Lentigen Corp., developed what it calls "a powerful new technology platform that expands applications for RNAi (RNA interference) to critical fields of life sciences research, including neuroscience, immunology and stem cell biology."
This advancement—going under the tongue-twisting name Thermo Scientific Dharmacon SMARTvector shRNA Lentiviral Particles—combines Thermo Scientific's gene-silencing technologies with Lentigen's expertise in viral delivery systems. SMARTvector reportedly will help researchers overcome common challenges faced when using RNAi, leading to permanent gene silencing in a wide range of cell types.
In this effort, researchers at Thermo applied innovations in RNAi to develop a novel, dedicated shRNA (short-hairpin RNA) design algorithm that is said to be key to the SMARTvector platform. The algorithm uses criteria unique to shRNA-based silencing for the routine production of highly functional sequences specific to every gene in human, mouse and rat genomes.
"Since our earliest days of RNAi work, we've been a leader in technological development, but we specifically had wanted to hold back on developing and releasing a shRNA lentiviral vector technology until we thought we could produce a functional and highly reliable product," says Michael Deines, vice president of sales and marketing for Dharmacon Products at Thermo Fisher. "We have felt that previous products on the market lacked certain attributes that researchers needed or didn't work in many people's hands. And we felt we would rather wait until we could identify the best partner in the lentiviral space and release a fully functional product."
Deines says that some of the problems with technology up to this point have been a lack of ability to effectively deliver silencing sequences into cells and produce a high degree of knockdown.
"So researchers would be told they might have to try five or six or seven different shRNA vectors to find one that works," Deines says. "Also, earlier products have often required substantial amounts of handling or processing by researchers prior to them being able to use them, and often those researchers don't have the experience in working with lentivirals to produce viral products at a high enough titer to be useful in their experiments.
"One of our great frustrations has been to watch researchers spend enormous amounts of money on shRNA products that don't work in their hands or that require so much additional processing that they become impractical."
"With the SMARTvector advancement, we can now effectively deliver stably expressed gene silencing sequences into a broad range of cell types, including those that are difficult to work with, such as primary cells, non-dividing cells, stem cells and neuronal cell lines," said Dr. Ian Jardine, vice president of global research and development for Thermo Fisher Scientific, in a news release about the deal. "Scientists using these cell lines can now harness the power of RNAi in their research, overcoming fundamental limitations in certain existing technologies."
By combining shRNA with Lentigen's proprietary viral vector delivery system, the gene silencing sequence is integrated into the host cell genome, creating "permanent gene silencing that cannot be achieved with synthetic si-RNAs," the two companies report. Permanent gene silencing, they note, is crucial in many types of experiments, including those that examine complex gene networks in drug development and neurobiology.
"By linking Lentigen's lentiviral technology and production capabilities with the RNAi expertise of Thermo Fisher Scientific, we are giving scientists a new tool that enables a much broader range of experiments involving gene silencing," says Dr. Boro Dropulic, founder and chief executive officer of Lentigen.