Following its acquisition of Belgian RNA manufacturer RNA-Tec last autumn, Integrated DNA Technologies has begun positioning itself as the go-to source for mid-scale RNA manufacturing services for researchers looking to step up their early-stage work to in vivo testing.
Prior to the acquisition, IDT’s RNA-manufacturing capabilities were limited to the microgram-to-milligram range, which is considered small scale for drug development, Mark Behlke, vice president of molecular genetics at IDT, told RNAi News this week.
“RNA-Tec, on the other hand, has specialization in … mid-scale [manufacturing], which ranges from 10 milligrams up to around 10 grams of RNA,” he said. “This is the kind of yield of product you need for small animal studies — preclinical kind of work for drug development or basic research.”
At the same time, IDT is laying the groundwork to expand into the RNAi delivery field, building upon RNA-Tec’s prior work with targeting ligands.
“Delivery is going to end up being one of the crucial areas for realizing the benefits of RNAi both for therapeutics and for basic research,” Behlke said. “So we are looking to be involved with other partners who have delivery tools that they are interested in making available to the research market,” in addition to marketing delivery reagents developed in-house at IDT.
Prior to the advent of RNAi, IDT was “fairly self-sufficient” in meeting the demand for both DNA, which the company can produce in multi-gram quantities, and RNA synthesis, Behlke explained. It wasn’t until siRNAs came onto the scene that the field started seeing RNA orders routinely coming in at the gram-scale and higher.
With the widespread adoption of RNAi, “there suddenly became a demand for … mid- to large-scale manufacturing for RNA, [which] was something we didn’t have direct expertise ourselves in,” he said. “Rather than re-invent the wheel, we aligned … with RNA-Tec.”
According to Brian Sproat, RNA-Tec’s CSO, the IDT unit currently synthesizes “hundreds of milligrams to multi-grams for several biotechs,” and there is significant interest coming from the pharmaceutical field now that “people have finally figured out how to minimize off-target effects and deliver these” RNAi molecules.
Although large-scale RNA manufacturing of the kind required for clinical studies is beyond IDT’s grasp, even with RNA-Tec under its corporate umbrella, the company said it can still offer a full range of synthesis services.
Large-scale manufacturing “is really something quite different because there you’re dealing not only with a very large scale, you’re dealing with pharmaceutical-grade material,” Behlke conceded. However, should one of the company’s clients eventually require quantities of RNA beyond what IDT can handle, the company would pass off the job to a cGMP collaborator such as Lonza, which formed a non-exclusive alliance with RNA-Tec in 2004.
With such deals in place, “we cover the entire field the way through from basic discovery to clinical development,” Sproat said.
In addition to its existing RNA manufacturing customers, which are undisclosed due to confidentiality agreements, IDT hopes to find new clients among those interested in its Dicer-substrate technology.
Developed in collaboration with the City of Hope’s Beckman Research Institute, IDT’s Dicer-substrates are synthetic RNA duplexes between 25 and 30 nucleotides long capable of triggering RNAi silencing. Already one RNAi drug developer, Nastech Pharmaceuticals, has taken a license to use the technology for therapeutic applications (see RNAi News, 11/9/2006).
IDT COO Trey Martin told RNAi News that his company is a supplier of Dicer-substrate molecules to research labs at BRI. Behlke added that Nastech, while it has its own internal manufacturing capability, has outsourced “its overflow to us.”
In addition, IDT sees “people who are going from academia to biotech and want to develop [RNA-based] therapeutics,” whether they be siRNAs, aptamers, antisense, or locked nucleic acids, as a source of potential clients, Sproat noted.
In conjunction with establishing itself as a key RNA manufacturer, “we’re also trying to make a big mark in the field of in vivo target validation, which means we have to look at delivery technologies,” Sproat said.
“RNA-Tec, on the other hand, has specialization in … mid-scale [manufacturing], which ranges from 10 milligrams up to around 10 grams of RNA. This is the kind of yield of product you need for small animal studies — preclinical kind of work for drug development or basic research.”
According to Martin, IDT is planning on introducing a “menu of [targeted delivery] options for our customers that would obviously include our in vivo-ready synthesis and prep, along with either ligand attachment for specific in vivo targeting or perhaps compartmentalization in different kinds of particles.”
The company expects to launch these offerings by the third quarter of 2007, although Behlke noted that “the science is going to have to dictate” the exact timing.
“The launch time will also dictate the breadth of the menu,” Martin added. “We’d like to get it as broad as we can before we go public with it, but nonetheless if it takes too long on one front or another we can launch with three or four focused target possibilities and grow it on an ongoing basis.”
This menu of delivery technologies is expected to ultimately include ones developed by IDT, as well as ones licensed from outside sources.
“We have [in-house] programs … already in place, but we are very open to working with people, particularly those that are willing to make their reagents available to the research market,” Behlke said, noting that IDT already has some collaborations with academic and corporate partners in progress.
“There have been a lot of publications that have come up over the past couple of years showing some nice delivery tools, but many of these are tied up in therapeutic development programs and are not available to most researchers,” he said. Through partnerships, IDT hopes to change that.