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yeh i'm liking this story. it's a nice bit of practical "industrialist" know-how

improving shRNA development, which is what it needs to get others going on it.


Greg Hannon and CSHL are right up there in the rarified Rossi atmosphere.

i recall something about he allegedly missed out on a getting a seminal shRNA

patent due to some allegedly tardy patent prosection work.


anything that supercharges the early lab work also translates to

improved viability and so more groups able to go after shRNA molecules


even doug macron likes it:


CSHL Team Publishes Method for Large-Scale Identification of Potent shRNAs

February 24, 2011 By Doug Macron


Researchers from Cold Spring Harbor Laboratory this week published details of a new method to identify potent shRNAs on a large scale, which they say also provides "new insights into sequence requirements of effective RNAi."


While shRNAs are "powerful experimental tools" for gene silencing, the requirements for "efficient shRNA biogenesis and target suppression are largely unknown ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’â€Å¡Ãƒƒâہ¡ÃƒÆ’‚¦ [and as a result] many predicted shRNAs fail to efficiently suppress their target," the team, lead by CSHL researchers Greg Hannon and Scott Lowe, wrote in Molecular Cell.


This, they noted, can lead to false-negative results in functional studies and screens. To address the issue, they developed a so-called sensor assay that enables the "biological detection" of effective shRNAs.


"Our approach measures the potency of shRNAs by monitoring their interaction with a surrogate target cloned into the 3' UTR of a fluorescent reporter, and thus integrates most aspects of shRNA biogenesis, target recognition, and repression," the team stated in the paper.


"Combining on-chip synthesis of long oligonucleotides with a two-step cloning procedure, we generated a library of [about] 20,000 shRNA-sensor constructs representing almost every target site in nine mammalian transcripts," they explained. "Using genetically distant avian reporter cells, we simultaneously evaluated the potency of every shRNA within this library via iterative cycles of FACS-based enrichment and deep sequencing-based quantification, and thereby established a straightforward protocol for identifying potent shRNAs in a multiplexed format."


The team noted that the method accurately predicts the activity of shRNAs toward endogenous targets and "reliably" identifies hairpins that are effective when expressed from a single genomic integration. Their approach, they added, "vastly outperforms" existing siRNA-based algorithms, which miss more than 70 percent of the sensor-derived shRNAs "and generally necessitate the testing of many predictions to identify even a single potent shRNA."


The CSHL investigators also wrote in Molecular Cell that the shRNA-sensor method, while designed with potency in mind, may also address RNAi specificity issues. "First, our assay helps to control for sequence-specific off-target effects by enabling the identification of multiple potent shRNAs against any gene," they stated. "Second, it will reduce passenger-mediated off-target effects by selecting potent shRNAs with a bias for incorporating the intended guide strand into RISC."


The identification parameters guiding Drosha/DGCR8 processing, a component of the microRNA pathway, will also help minimize off-target effects associated with aberrant guide strands, while the assay's identification of single-copy shRNAs "should further reduce off-target toxicities owing to saturation of the RNAi machinery," they added.


"Our approach lays out a practical workflow for the rapid generation of functionally validated shRNA libraries, as well as the identification of potent RNAi triggers for biological studies and, eventually, RNAi therapeutics," they concluded.

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i'd defer the Enu on this - he's got the best grasp on the science handles.


He's has declared himself as a happy lurker. We can't expect any input from that. I'm afraid the job falls to you drafter. You have always been happy to share your intimate knowledge of the 099 process, you must have an opinion on the Patent Ammendment Act surely.

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when the process is completed we will have an idea of the consequences.


Here is some information going forward:




Critics Taking Aim At Senate Patent Bill Through Amendments


When the Patent Reform Act of 2011 reaches the Senate floor on Monday, analysts predict it will face amendments seeking to strip away some of the bill's most controversial proposals.


Now lobbyists familiar with discussions about the legislation say Senate Majority Leader Harry Reid, D-Nev., may support or even cosponsor a likely amendment by Sen. Diane Feinstein, D-Calif., which would remove a provision that would grant patents on a "first to file" rather than "first to invent" basis.


Under the bill, which is sponsored by Judiciary Chairman Patrick Leahy, D-Vt., if a certain product is almost simultaneously invented by separate people, patent protection would be awarded to the first applicant to file for a patent on the product, rather than whoever is determined to have actually invented the product first.


Feinstein's amendment was briefly discussed but not voted on when the bill was approved by the Judiciary Committee in January.


Reid, who has not publicly weighed in on one side or another, has been lobbied for years by groups in his home state of Nevada, said Tim Casey, a partner at SilverSky Group, a Reno-based intellectual property firm.


"Despite all the casinos, 95 percent of Nevadans are employed by small businesses," Casey said. "The first-to-file change could likely have a greater impact on small businesses than any other part of that legislation. And Senator Reid has been pretty aggressive in seeking input from his state on this issue."


Casey said he met last week with Reid staffers and he welcomed any potential support from the senator. A Reid spokesman did not immediately respond to a request for comment.


Some small businesses have argued that they rarely have the resources or money to rush to the U.S. Patent and Trademark Office, which means a first-to-file system gives larger companies an advantage. On Wednesday several small business associations sent a letter to Reid and the rest of the Senate specifically targeting the first-to-file proposal in Leahy's bill.


Other likely amendments include measures that would allow the Patent and Trademark Office to keep all its fees, as well as restrict so-called business-method patents.


Despite the criticism, Leahy insists the bill enjoys broad support, touting a long list of companies and associations that have signed on to the measure.

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plastic I think you are more interested in this one..


The Patentability of Biological Materials in Australia


The Bill seeks to ban the patenting of all biological material that is ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’â€Â¦ÃƒƒÂ¢Ãƒ¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…âہ“identical or substantially identical to such materials as they exist in natureÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’â€Å¡Ãƒƒâہ¡ÃƒÆ’‚ÂÂ. If passed, this legislation may significantly jeopardize the biotechnology, pharmaceutical, medical and agricultural industries in Australia.



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I'd like to draw your attention to a post on Hotcopper:




New research by Greg Hannon has found a way to test thousands of potential shRNAi candidates at once. A problem plaguing RNAi researchers is the difficulty of finding the roughly 2.5% of all possible shRNAs against that gene could shut down its activity efficiently. This method powerfully advances RNAi technology, making target selection systematic and much less random.


And guess what? It appears that this method is at least partly under license from Benitec! Noticing that the method described in the above is very similar to the way Benitec does it's RNAi research (using retroviral vectors with shRNAi) I did a Google search for Gregory Hannon and Benitec and look what I came up with!




What a clever fellow this "Dank" is ... Greg Hannon has been making alot of progress in bring shRNA technology to the front and centre of drug development:



Permitted Use. Portions of this product are covered by published patent applications (the "shRNA

IP Rights") owned by Cold Spring Harbor Laboratory, referred to herein as ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’â€Â¦ÃƒƒÂ¢Ãƒ¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…âہ“CSHL.ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’â€Å¡Ãƒƒâہ¡ÃƒÆ’‚ This product,

and/or any components or derivatives of this product, and/or any materials made using this product

or its components, are referred to herein as the ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’â€Â¦ÃƒƒÂ¢Ãƒ¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…âہ“Product.ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’â€Å¡Ãƒƒâہ¡ÃƒÆ’‚ Subject to the terms of this Limited Use

Agreement, sale of the Product by Open Biosystems (ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’â€Â¦ÃƒƒÂ¢Ãƒ¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…âہ“OBSÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’â€Å¡Ãƒƒâہ¡ÃƒÆ’‚ÂÂ) conveys the limited, nonexclusive,

nontransferable right to any company or other entity that orders, pays for and takes delivery of the

Product (the ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’â€Â¦ÃƒƒÂ¢Ãƒ¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…âہ“CustomerÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’â€Å¡Ãƒƒâہ¡ÃƒÆ’‚ÂÂ) from OBS to use the Product solely for its internal research and only at

such CustomerÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¾Ãƒâہ¡ÃƒÆ’‚¢s facility where the Product is delivered by OBS.


But is looks like this new shiny technology needs a "foundation" technology license ...


Limited Label License: Benitec

This product is sold solely for use for research purposes in fields other than plants. This product is

not transferable. If the purchaser is not willing to accept the conditions of this label license,

supplier is willing to accept the return of the unopened product and provide the purchaser with a

full refund. However, if the product is opened, then the purchaser agrees to be bound by the

conditions of this limited use statement. This product is sold by supplier under license from Benitec

Australia Ltd and CSIRO as co-owners of U.S. Patent No. 6,573,099 and foreign counterparts. For

information regarding licenses to these patents for use of ddRNAi as a therapeutic agent or as a

method to treat/prevent human disease, please contact Benitec at licensing@benitec.com. For the

use of ddRNAi in other fields, please contact CSIRO at www.pi.csiro.au/RNAi.

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In commercial revenue terms what does that mean exactly?


It appears to me to be some kind of business model based on the Linux concept. I don't know if Linux ever made a bean since its whole purpose was to rival MSFT's OS.


I just can't imagine every household in the western world wanting a licence for ddRNAi the same way they wanted one for Windows 95 or Microsoft Office.


Good news nevertheless in an ISIS kind of way. They have been listed for twenty years and are now cheaper than they have ever been.


All things aside, one would expect disclosure of such things to be in the domain of management since revenues are highly relevant to the fate of this company when so far we are led to believe their fate rests with La Jolly.

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I just can't imagine every household in the western world wanting a licence for ddRNAi the same way they wanted one for Windows 95 or Microsoft Office.


but we know there's plenty of households that would be happy to pay for better therapies for a whole raft

of diseases including cancers, diabetes, neuro, etc. And if the makers of these better drugs needed a ddRNAi licence, sweet.

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the thrust of the human gene patent discussion is whether human genes can be

patented, given they are part of our heredity. fair enough. see the myriad case

where a naturally occuring onco gene for breast cancer was patented and any hospital

testing for it needed to pay myriad $2100. bit harsh really.


RNAi molecules, which aren't human genes, is a different argument which opens

up too many gaps on the antagonists side. the attempts to include RNAi in the argument

are really drawing a longbow.


moreover, the method by which you create the RNAi (ddRNAi) is totally defendable,

and that's what Graham '099 provides.

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