New RNAi Tools Enable Systematic Studies Of Gene Function

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New RNAi Tools Enable Systematic Studies Of Gene Function

http://www.medicalnewstoday.com/medicalnews.php?newsid=40250

An international public-private research team led by scientists at

the Broad Institute of MIT and Harvard announced today the

construction and availability of an extensive library of molecular

reagents to silence most human and mouse genes. As described in the

March 24 issue of Cell, this library consists of small RNA molecules

that can switch off genes individually, allowing the user to dissect

the genetic underpinnings of normal biology and disease. These RNA-

interference (RNAi)-based gene inhibitors are packaged in

lentiviruses, enabling their use in virtually all types of human and

mouse cells. This work springs from the RNAi Consortium (TRC), a

unique collaboration among academic research institutions and leading

life science companies with the mission to build comprehensive RNAi

libraries and make them available to scientists worldwide.

" Switching off a single gene through RNAi reveals how that gene

functions in a particular biological process. When RNAi's potential

is applied to thousands of genes - as it has been in fruit flies and

nematodes - it can provide a more complete picture of that process, "

said Root, a senior author of the Cell paper and the director

of TRC and the RNAi platform at the Broad Institute. " Thanks to this

unique public-private effort, we now have new tools to enable the

entire research community to realize the potential of RNAi in the two

most important species in biomedicine. "

" The RNAi library developed by TRC is a rich resource for biological

discovery, " said Nir Hacohen, assistant professor at Massachusetts

General Hospital and Harvard Medical School, associate member of the

Broad Institute and a senior author. " Ongoing studies in my own

laboratory to understand how the immune system senses pathogens and

appropriately targets its response will be accelerated using these

tools. "

RNAi gives scientists the ability to turn off an individual gene. Its

workhorses are small RNA molecules, each of which is tailored to

match a fragment of a gene's unique DNA. This RNA can then bind to

its gene target, rendering it inactive. In order to get the small

RNAs into cells, TRC scientists packaged them in

lentiviruses. " Across the spectrum of biomedicine, there is a need

for tools that can be applied to diverse cell types. This is

particularly true in cancer research, " said Bill Hahn, assistant

professor at Dana-Farber Cancer Institute and Harvard Medical School,

associate member of the Broad Institute and a senior author of the

study. " For TRC's library, lentiviral delivery is an especially

effective means to meet this need. "

The parallel analysis of thousands of genes using RNAi allows

researchers to more readily pinpoint the genes that control a

biological process. Therefore, TRC developed the high-throughput

techniques and quality-control measures required for such genome-

scale studies. " It is a distinct challenge to achieve consistent and

cost-effective RNAi methods and we placed a strong emphasis on this

part of the process, " said Sabatini, member of Whitehead

Institute for Biomedical Research, assistant professor at

Massachusetts Institute of Technology, associate member of the Broad

Institute and a senior author. " In the quest to develop comprehensive

tools for gene discovery in mice and humans, this technology will be

a key piece in the puzzle. "

To evaluate the RNAi library's performance, the scientists sampled a

subset that targets approximately 1,000 human genes. They

systematically inactivated these genes in a human cancer cell line to

identify ones that regulate cell division during malignancy.

Automated cellular imaging was used to efficiently identify dividing

cells in thousands of samples. This approach uncovered more than 100

previously unknown growth regulators in addition to several known

players, confirming the library's sensitivity as a vehicle for gene

discovery.

" This critical new tool illustrates the requirement for academic and

industry partnerships to drive scientific innovation, " said

Lander, director of the Broad Institute and a senior author. " The

importance of putting these reagents in the public domain will be

demonstrated by the many important biomedical discoveries that will

stem from them. "