Second Phase SBIR Contract from the National Cancer Institute (NCI) to Identify Lethal Gene Combinations in Cancer Cell Models

It's been a while since the last post to this blog. It is not that nothing has been going on, in fact, quite the opposite. It has been quite busy the past several months and, unfortunately, blog postings have suffered. However, I thought I would get things started again with short post about our recent SBIR Contract.

Cellecta has been awarded an SBIR Phase II Contract from the NIH National Cancer Institute to continue its work using RNAi screens to identify paired combinations of DNA damage and repair (DDR) genes essential for cancer cells. Some results from the first phase of the grant were posted previously: /blog/2011/08/31/rnai-screen-cancer-synergistic-lethality. That work was essentially a proof of principle targeting combinations of 40 DDR genes. With this continuation of the contract, we can now move into a full scale screen of over 400 different DDR genes and run the screen in multiple cell models so we can identify which gene combinations are essential in each.

The purpose of the screen is to identify synthetic lethal genes--genes that, when inactivated together, have a significantly stronger lethal effect than when either is inactivated alone. The idea is that combination therapies could be developed using drugs that target both of the genes together. This combination approach makes is less likely for cancer cells to develop resistance to treatment.

With array based screening, however, it is extremely resource and labor intensive to identify these lethal combinations. However, a pooled RNAi screening approach using a library that co-expresses pairs of shRNAs targeting all combinations of the DDR genes enables efficient screens of tens of thousands of combinations.

We are making the dual shRNA expression libraries now and looking forward to getting these combinational screens started as soon as possible. As soon as we have something interesting, I'll post it here—so keep an eye out for updates.

You can read the press release about Cellecta's new SBIR Contract at

Please email with any comments.

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