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New gene-editing system enables large-scale studies of gene function.

Discussion in 'Other Health News and Research' started by Waverunner, Dec 27, 2013.

  1. Waverunner

    Waverunner Senior Member

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    CRISPR, a new way to edit genes, could become very useful for gene therapy. When I read these articles, I have to wonder however, if scientists are interested in curing patients or are more focused on understanding biology. It's great, that they want to understand diseases but one has to wonder, why they seem to love treating a disease and not preventing or curing it.

    I can give you a perfect example. The article says: "In future studies, the researchers plan to conduct genomewide screens of cells that have become cancerous through the loss of tumor suppressor genes such as BRCA1. If scientists can discover which genes are necessary for those cells to thrive, they may be able to develop drugs that are highly cancer-specific, Wang says."

    BRCA1 is a gene, that repairs DNA double strand breaks. If this gene is not working, more mutations occur and the risk for driver mutations and cancer increases up to a lifetime risk for breast cancer of 85% (at least this is, how I understood it). So a main goal should be, to replace the faulty BRCA gene because then DNA repair will function normally and cancer risk will be highly reduced.

    But instead of repairing the faulty BRCA gene and preventing breast cancer, they look at methods to improve chemotherapy and targeted cancer therapy. This is very important for already diagnosed breast cancer patients but it is a joke for any women with BRCA mutations because instead of preventing you from getting cancer, they only improve the therapy. And even if you are disease free after chemotherapy, with a BRCA mutation you are very likely to suffer from recurrence very soon. So it will be a cycle of cancer - therapy - cancer - therapy - cancer etc..
    A much better approach would be: BRCA mutation - repair faulty BRCA gene with CRISPR - no breast cancer or highly reduced risk.

    Don't get me wrong, it's good if we have better therapies, but these therapies will take 10 to 20 to 30 years, if they are approved at all. In order to get rid of many health care problems, a much easier approach would be to do one thing: Look at healthy people, find out how healthy genes look like (we already know this to a high degree). Insert these healthy genes into ill people with high risk genes. Job done. There is no need to develop new genes or understand them to the molecular level. We just copy what nature already planned to keep humans healthy.


    http://web.mit.edu/newsoffice/2013/speeding-up-gene-discovery-1212.html

    Since the completion of the Human Genome Project, which identified nearly 20,000 protein-coding genes, scientists have been trying to decipher the roles of those genes. A new approach developed at MIT, the Broad Institute, and the Whitehead Institute should speed up the process by allowing researchers to study the entire genome at once.

    The new system, known as CRISPR, allows researchers to permanently and selectively delete genes from a cell’s DNA. In two new papers, the researchers showed that they could study all the genes in the genome by deleting a different gene in each of a huge population of cells, then observing which cells proliferated under different conditions.

    “With this work, it is now possible to conduct systematic genetic screens in mammalian cells. This will greatly aid efforts to understand the function of both protein-coding genes as well as noncoding genetic elements,” says David Sabatini, a member of the Whitehead Institute, MIT professor of biology, and a senior author of one of the papers, both of which appear in this week’s online edition of Science.

    Using this approach, the researchers were able to identify genes that allow melanoma cells to proliferate, as well as genes that confer resistance to certain chemotherapy drugs. Such studies could help scientists develop targeted cancer treatments by revealing the genes that cancer cells depend on to survive.

    Feng Zhang, the W.M. Keck Assistant Professor in Biomedical Engineering in the Department of Brain and Cognitive Sciences and senior author of the other Sciencepaper, developed the CRISPR system by exploiting a naturally occurring bacterial protein that recognizes and snips viral DNA. This protein, known as Cas9, is recruited by short RNA molecules called guides, which bind to the DNA to be cut. This DNA-editing complex offers very precise control over which genes are disrupted, by simply changing the sequence of the RNA guide.

    “One of the things we’ve realized is that you can easily reprogram these enzymes with a short nucleic-acid chain. This paper takes advantage of that and shows that you can scale that to large numbers and really sample across the whole genome,” says Zhang, who is also a member of MIT’s McGovern Institute for Brain Research and the Broad Institute.

    ...

    In future studies, the researchers plan to conduct genomewide screens of cells that have become cancerous through the loss of tumor suppressor genes such as BRCA1. If scientists can discover which genes are necessary for those cells to thrive, they may be able to develop drugs that are highly cancer-specific, Wang says.

    This strategy could also be used to help find drugs that counterattack tumor cells that have developed resistance to existing chemotherapy drugs, by identifying genes that those cells rely on for survival.

    The researchers also hope to use the CRISPR system to study the function of the vast majority of the genome that does not code for proteins. “Only 2 percent of the genome is coding. That’s what these two studies have focused on, that 2 percent, but really there’s that other 98 percent which for a long time has been like dark matter,” Sanjana says.
     
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  2. Hip

    Hip Senior Member

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    In 200 years, perhaps there will be a technology that can edit and repair human genes in each of the 30 trillion odd cells in the human body, but gene therapy today is limited.

    Though I suspect that within 50 years, faulty genes may be edited and repaired at conception, when the fetus is still just one cell. Although that would likely mean using an in vitro fertilization technique to begin with.
     
    Last edited: Dec 27, 2013
  3. Waverunner

    Waverunner Senior Member

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    In my eyes your prediction is way off the tracks and with way off I mean somebody locating Paris on Mars, rather than in France. Just for your understanding, gene therapy for LPLD has already been approved in Europe. http://www.uniqure.com/products/glybera/

    They use an "old fashioned" viral vector in this case. I have no idea, when the development of this therapy started but it probably was some 5 to 10 years ago. However, our understanding of genetics improves tremendously every year, so who knows, what we are already able to do. The LPL gene has around 65,000 base pairs, BRCA has a lot more but I don't see, why we should not be able to replace it someday in the near future.
     
  4. Simon

    Simon

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    Monmouth, UK
    I think that the answer to you question is that the techniques they have developed are for deleting genes in for lab-grown cell cultures, which makes it a great tool for discovering which genes are crucial for tumours to thrive. It doesn't give them a way to change the faulty genes eg BRCA1 in sick people. That's why they are using this technique to better understand what goes wrong in cancer and then target those genes (or their products) that are to blame.

    I suspect that if they could repair faulty genes in sick patients, they would do so and await their Nobel prize :)

    Overall, though, this is an astonishing development: the ability to knock out any chosen gene - or even a combination of genes - provides an immensely powerful tool for studying diseases, including hopefully, one day, mecfs.

    added: Looks like they might be considering clinical applications:
     
    Last edited: Dec 28, 2013
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  5. Hip

    Hip Senior Member

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    A quick Google check finds that Gene therapy has been around for 25 years.

    I don't think that ethics committees will approve any gene therapy which edits germline cells for many decades, because of the unknown risks to future generations who will obviously inherit these edits.

    The gene therapy for LPLD you mentioned apparently (usually) does not add extra DNA to the human genome within the nucleus of each cell, but only adds some extra DNA to the cytoplasm of the cell. There is less risk of a cancer side effect if you refrain from editing the genome within the nucleus. 1

    I am not aware of any gene therapy that can go in and edit any desired section of the human genome.
     
    Last edited: Dec 28, 2013
  6. alex3619

    alex3619 Senior Member

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    Gene knockouts have been around for a very long time. Being able to do it faster, more reliably or cheaper is where the advantages may lie. Many knockout strains of mice have been used for many years in research. Indeed I was learning about this in 2000 or so.
     
  7. Hip

    Hip Senior Member

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    @alex3619
    That's very true, and of course a wealth of information comes from knockout mice studies. For example, if you want to figure out how a certain receptor works, you knockout the gene for that receptor, and then see how mice without that receptor function.

    But the ability to arbitrarily edit our own genes I can't imagine will arrive for ages. I certainly would like to edit all the SNP mutations that are present in my 23andme results. It would be great if you could just open a word processor document of your own genome, make all the necessary edits to your SNP mutations and other flaws in your genome, and then upload the corrected genome back into you body.
     
    Last edited: Dec 29, 2013
    Waverunner likes this.
  8. Waverunner

    Waverunner Senior Member

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    My question was pointed towards the development start of Glybera, not gene therapy in general but thanks for the answer.
     

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