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Thread: New Antibiotics?

  1. #1 New Antibiotics? 
    Moderator Moderator Cogito Ergo Sum's Avatar
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    In a previous thread of mine, I have stated that we are running out of antibiotics.
    As such, it is troublesome to know that there are bacteria out there that are resistant to a broad range of antibiotics, so they are posing a threat on our health.

    For example, take the CRE (Carbapenem-resistant Enterobacteriaceae), which have the highest threat level ("urgent") as put forward by the CDC:
    "Untreatable and hard-to-treat infections from carbapenem-resistant Enterobacteriaceae (CRE) bacteria are on the rise among patients in medical facilities. CRE have become resistant to all or nearly all the antibiotics we have today. Almost half of hospital patients who get bloodstream infections from CRE bacteria die from the infection."


    New antibiotics must be synthesized, but there might be better weapons with which we could defeat the threats of these tiny creatures: PPMOs.
    New evidence has shown that these molecules could serve as antibiotics:
    "The mechanism that PPMOs use to kill bacteria is revolutionary," said Bruce Geller, a professor of microbiology in the OSU College of Science and lead author on the study. "They can be synthesized to target almost any gene, and in that way avoid the development of antibiotic resistance and the negative impacts sometimes associated with broad-spectrum [i.e. useful against a wide variety of bacteria] antibiotics."


    More specifically, (Geller, B.L. et al., 2013) tested if PPMOs could kill Acinetobacter strains in mice who had a pulmonary infection.
    Acinetobacter are a group of bacteria that can cause a wide variety of diseases and are also resistant to a lot of antibiotics.

    PPMO stands for peptide-conjugated phosphorodiamidate morpholino oligomer, a synthetic analog of DNA (or RNA) that can silence gene expression.
    In other words, artificial strands of genetic material that can halt the synthesis of certain proteins by interfering with the RNA (i.e. the messenger between DNA and proteins) of the bacterium.
    An analysis (Summerton, J. et al., 1997) showed that these compounds have many advantages (e.g. safety, efficacy at low concentrations).


    Given the fact that the results from this study are quite promising, it would be an useful method to reduce the level of mortality of CRE bacteria infections.
    Yet, human trials have not yet been conducted. Do you think that the government should invest in this research to tackle the shortage of antibiotics?


    Sources:
    Threat Report 2013 - CDC
    Beyond antibiotics: 'PPMOs' offer new approach to bacterial infection, other diseases
    Geller, B.L. et al. (2013), "Gene-Silencing Antisense Oligomers Inhibit Acinetobacter Growth In Vitro and In Vivo", J Infect Dis 208(9)
    CDC - Acinetobacter in Healthcare Settings - HAI
    Summerton, J. et al. (1997), "Morpholino Antisense Oligomers: Design, Preparation, and Properties", Antisense & Nucleic Acid Drug Dev 7, pp. 187-195


    PS: Carbapenems are a certain class of antibiotics.


    Last edited by Cogito Ergo Sum; April 7th, 2014 at 06:28 AM. Reason: RNA, not genome.
    "The only safe rule is to dispute only with those of your acquaintance of whom you know that they possess sufficient intelligence and self-respect not to advance absurdities; to appeal to reason and not to authority, and to listen to reason and yield to it; and, finally, to be willing to accept reason even from an opponent, and to be just enough to bear being proved to be in the wrong."

    ~ Arthur Schopenhauer, The Art of Being Right: 38 Ways to Win an Argument (1831), Stratagem XXXVIII.
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    Northern Horse Whisperer Moderator scheherazade's Avatar
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    Given that many people have allergies to antibiotics that even further limits their options for treatment of infections, I would consider this a wise use of research dollars.

    The increasing stresses of a population living in close proximity will only increase the opportunity for infections to spread IMO. The ability of bacteria to replicate and mutate will ever elude our ability to mitigate unless we can identify the means to interfere with the actual mechanism of change, not it's product, as I see it. While bacteria specific antibiotics may be of financial benefit to the drug companies, they are not the most efficient way to treat the patient as first one, then another antibiotic is utilized, paving the path for future immunity by bacteria.


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    Forum Masters Degree mat5592's Avatar
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    I've always liked to say Acinetobacter baumannii out loud. Not that it's relevant
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    Quote Originally Posted by mat5592 View Post
    I've always liked to say Acinetobacter baumannii out loud. Not that it's relevant
    its something Caesar or alexander the great would say scream before battle...
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    Northern Horse Whisperer Moderator scheherazade's Avatar
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    Quote Originally Posted by mat5592 View Post
    I've always liked to say Acinetobacter baumannii out loud. Not that it's relevant
    It has a 'catchy' sound to it...just seems to roll off the tongue...
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  7. #6  
    Northern Horse Whisperer Moderator scheherazade's Avatar
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    Quote Originally Posted by blackscorp View Post
    Quote Originally Posted by mat5592 View Post
    I've always liked to say Acinetobacter baumannii out loud. Not that it's relevant
    its something Caesar or alexander the great would say scream before battle...

    LOL....

    Is 'Carpe Diem' contagious?
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  8. #7  
    Forum Masters Degree mat5592's Avatar
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    Does a different PPMO need to be developed for each type of bacteria that needs to be treated? For example, is the PPMO used in the study only specific to Acinetobacter? That could be a good and bad thing. Bad, because well, you'd have to develop it for a multitude of genera, which would be expensive. Good, because if it were specific, you wouldn't have to really worry about destroying normal flora like you do with most antibiotics today.
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  9. #8  
    Forum Masters Degree mat5592's Avatar
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    Quote Originally Posted by scheherazade View Post
    Quote Originally Posted by mat5592 View Post
    I've always liked to say Acinetobacter baumannii out loud. Not that it's relevant
    It has a 'catchy' sound to it...just seems to roll off the tongue...
    Kind of like Haemophilus aphrophilus did...but then they changed it to Aggregatibacter aphrophilus
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  10. #9  
    Moderator Moderator Cogito Ergo Sum's Avatar
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    Quote Originally Posted by mat5592 View Post
    Does a different PPMO need to be developed for each type of bacteria that needs to be treated? For example, is the PPMO used in the study only specific to Acinetobacter? That could be a good and bad thing. Bad, because well, you'd have to develop it for a multitude of genera, which would be expensive. Good, because if it were specific, you wouldn't have to really worry about destroying normal flora like you do with most antibiotics today.

    It does not seem to be necessary to produce a new type of PPMO for every strain.
    A previous experiment with E. coli (Mellbye, B.L. et al, 2009) has shown that these bacteria are also sensitive for (RXR)4-AcpP.
    The PPMO attacks the same RNA strand that codes for the essential protein (AcpP).

    However, I do think that it is necessary to keep in mind that you must specifically target the bacterium without destroying the normal flora.
    DNA sequencing could bring forth a solution for this problem.
    Yet, the PPMO might be useful, given the fact that E. coli live in your intestines whilst A. baumannii attacks your lungs.


    PS: I have Googled the A. aphrophilus. That is a nasty species.
    "The only safe rule is to dispute only with those of your acquaintance of whom you know that they possess sufficient intelligence and self-respect not to advance absurdities; to appeal to reason and not to authority, and to listen to reason and yield to it; and, finally, to be willing to accept reason even from an opponent, and to be just enough to bear being proved to be in the wrong."

    ~ Arthur Schopenhauer, The Art of Being Right: 38 Ways to Win an Argument (1831), Stratagem XXXVIII.
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    Quote Originally Posted by scheherazade View Post
    Quote Originally Posted by blackscorp View Post
    Quote Originally Posted by mat5592 View Post
    I've always liked to say Acinetobacter baumannii out loud. Not that it's relevant
    its something Caesar or alexander the great would say scream before battle...

    LOL....

    Is 'Carpe Diem' contagious?
    a bit contagious I don't know how to post a pic from computer...
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  12. #11  
    Moderator Moderator Cogito Ergo Sum's Avatar
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    Quote Originally Posted by blackscorp View Post
    Quote Originally Posted by scheherazade View Post
    Quote Originally Posted by blackscorp View Post
    Quote Originally Posted by mat5592 View Post
    I've always liked to say Acinetobacter baumannii out loud. Not that it's relevant
    its something Caesar or alexander the great would say scream before battle...

    LOL....

    Is 'Carpe Diem' contagious?
    a bit contagious I don't know how to post a pic from computer...

    Go to TinyPic, upload your picture, copy the URL and paste it in your thread via the "Image" button in your "Quick Reply" editor.
    "The only safe rule is to dispute only with those of your acquaintance of whom you know that they possess sufficient intelligence and self-respect not to advance absurdities; to appeal to reason and not to authority, and to listen to reason and yield to it; and, finally, to be willing to accept reason even from an opponent, and to be just enough to bear being proved to be in the wrong."

    ~ Arthur Schopenhauer, The Art of Being Right: 38 Ways to Win an Argument (1831), Stratagem XXXVIII.
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    Quote Originally Posted by Cogito Ergo Sum View Post
    Quote Originally Posted by blackscorp View Post
    Quote Originally Posted by scheherazade View Post
    Quote Originally Posted by blackscorp View Post
    Quote Originally Posted by mat5592 View Post
    I've always liked to say Acinetobacter baumannii out loud. Not that it's relevant
    its something Caesar or alexander the great would say scream before battle...

    LOL....

    Is 'Carpe Diem' contagious?
    a bit contagious I don't know how to post a pic from computer...

    Go to TinyPic, upload your picture, copy the URL and paste it in your thread via the "Image" button in your "Quick Reply" editor.
    I meant directly from pc... without need for upload to other site
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  14. #13  
    Forum Masters Degree mat5592's Avatar
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    Quote Originally Posted by Cogito Ergo Sum View Post
    Quote Originally Posted by mat5592 View Post
    Does a different PPMO need to be developed for each type of bacteria that needs to be treated? For example, is the PPMO used in the study only specific to Acinetobacter? That could be a good and bad thing. Bad, because well, you'd have to develop it for a multitude of genera, which would be expensive. Good, because if it were specific, you wouldn't have to really worry about destroying normal flora like you do with most antibiotics today.

    It does not seem to be necessary to produce a new type of PPMO for every strain.
    A previous experiment with E. coli (Mellbye, B.L. et al, 2009) has shown that these bacteria are also sensitive for (RXR)4-AcpP.
    The PPMO attacks the same RNA strand that codes for the essential protein (AcpP).

    However, I do think that it is necessary to keep in mind that you must specifically target the bacterium without destroying the normal flora.
    DNA sequencing could bring forth a solution for this problem.
    Yet, the PPMO might be useful, given the fact that E. coli live in your intestines whilst A. baumannii attacks your lungs.


    PS: I have Googled the A. aphrophilus. That is a nasty species.
    True, you wouldn't necessarily need to administer the agent orally if it were a septic infection, lung infection, etc. Regardless, the idea that it would be much more difficult for the bacteria to become resistant is an exciting one. And for some reason, I see your PS in the quote but not in your post as I am typing this.
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  15. #14  
    Making antisense Jon Moulton's Avatar
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    The PPMO is a two-moiety molecule composed of an antisense Morpholino oligo and a cell-penetrating delivery peptide. The antisense oligos are targeted to conserved RNA sequence in an effort to avoid development of resistance. If resistance develops, you can vary the base sequence of the antisense oligo to compensate (though doing that medically would require new clinical trials). The current generation of cell-penetrating peptides are somewhat toxic, but the delivery moieties likely can be improved.
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  16. #15  
    Moderator Moderator Cogito Ergo Sum's Avatar
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    Quote Originally Posted by blackscorp View Post
    Quote Originally Posted by Cogito Ergo Sum View Post
    Quote Originally Posted by blackscorp View Post
    Quote Originally Posted by scheherazade View Post
    Quote Originally Posted by blackscorp View Post
    Quote Originally Posted by mat5592 View Post
    I've always liked to say Acinetobacter baumannii out loud. Not that it's relevant
    its something Caesar or alexander the great would say scream before battle...

    LOL....

    Is 'Carpe Diem' contagious?
    a bit contagious I don't know how to post a pic from computer...

    Go to TinyPic, upload your picture, copy the URL and paste it in your thread via the "Image" button in your "Quick Reply" editor.
    I meant directly from pc... without need for upload to other site

    I do not think that it is possible. Several other users (including me) have tried that, but it does not work.
    I do not know why some of us encounter difficulties.

    Quote Originally Posted by Jon Moulton View Post
    The PPMO is a two-moiety molecule composed of an antisense Morpholino oligo and a cell-penetrating delivery peptide. The antisense oligos are targeted to conserved RNA sequence in an effort to avoid development of resistance. If resistance develops, you can vary the base sequence of the antisense oligo to compensate (though doing that medically would require new clinical trials). The current generation of cell-penetrating peptides are somewhat toxic, but the delivery moieties likely can be improved.

    I was not aware of their toxicity. Thank you for pointing that out!
    "The only safe rule is to dispute only with those of your acquaintance of whom you know that they possess sufficient intelligence and self-respect not to advance absurdities; to appeal to reason and not to authority, and to listen to reason and yield to it; and, finally, to be willing to accept reason even from an opponent, and to be just enough to bear being proved to be in the wrong."

    ~ Arthur Schopenhauer, The Art of Being Right: 38 Ways to Win an Argument (1831), Stratagem XXXVIII.
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  17. #16  
    Northern Horse Whisperer Moderator scheherazade's Avatar
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    Quote Originally Posted by blackscorp View Post

    I meant directly from pc... without need for upload to other site
    You can upload to your own album at your profile page on this site and then link to it. I don't know about direct from your own computer otherwise.
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  18. #17  
    Northern Horse Whisperer Moderator scheherazade's Avatar
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    Quote Originally Posted by Jon Moulton View Post
    The PPMO is a two-moiety molecule composed of an antisense Morpholino oligo and a cell-penetrating delivery peptide. The antisense oligos are targeted to conserved RNA sequence in an effort to avoid development of resistance. If resistance develops, you can vary the base sequence of the antisense oligo to compensate (though doing that medically would require new clinical trials). The current generation of cell-penetrating peptides are somewhat toxic, but the delivery moieties likely can be improved.
    Welcome to this forum, Jon.

    You sound like you have some experience in this field. I just learned a new word, 'moieties'.
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  19. #18  
    Forum Masters Degree mat5592's Avatar
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    Quote Originally Posted by scheherazade View Post
    Quote Originally Posted by Jon Moulton View Post
    The PPMO is a two-moiety molecule composed of an antisense Morpholino oligo and a cell-penetrating delivery peptide. The antisense oligos are targeted to conserved RNA sequence in an effort to avoid development of resistance. If resistance develops, you can vary the base sequence of the antisense oligo to compensate (though doing that medically would require new clinical trials). The current generation of cell-penetrating peptides are somewhat toxic, but the delivery moieties likely can be improved.
    Welcome to this forum, Jon.

    You sound like you have some experience in this field. I just learned a new word, 'moieties'.
    In addition, his location is Corvallis, Oregon, the location of Oregon State University, where this particular study was published.

    Coincidence?!
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  20. #19  
    Moderator Moderator Cogito Ergo Sum's Avatar
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    Quote Originally Posted by mat5592 View Post
    In addition, his location is Corvallis, Oregon, the location of Oregon State University, where this particular study was published.

    Coincidence?!

    Perhaps not.
    The name "Jon D. Moulton (Ph.D.)" is frequently associated with the word "morpholino" (even in Google Scholar).
    According to this study (Kloosterman, W.P. et al., 2007), Jon D. Moulton is connected to Gene Tools, Philomath, Oregon.
    Jon Moulton likes this.
    "The only safe rule is to dispute only with those of your acquaintance of whom you know that they possess sufficient intelligence and self-respect not to advance absurdities; to appeal to reason and not to authority, and to listen to reason and yield to it; and, finally, to be willing to accept reason even from an opponent, and to be just enough to bear being proved to be in the wrong."

    ~ Arthur Schopenhauer, The Art of Being Right: 38 Ways to Win an Argument (1831), Stratagem XXXVIII.
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  21. #20  
    Making antisense Jon Moulton's Avatar
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    I did enter Gene Tools in my profile. I've been working with Morpholino antisense for almost 14 years now. My wife Hong invented the Morpholino-peptide conjugates at Sarepta Therapeutics (it was named AVI BioPharma back then); she's at Oregon State University now.

    We're both still working with Morpholinos. Our daughters suffer the dinner-table conversations.
    Last edited by Jon Moulton; October 16th, 2013 at 01:00 PM. Reason: expand thoughts
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  22. #21  
    Northern Horse Whisperer Moderator scheherazade's Avatar
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    Quote Originally Posted by Cogito Ergo Sum View Post
    Quote Originally Posted by mat5592 View Post
    In addition, his location is Corvallis, Oregon, the location of Oregon State University, where this particular study was published.

    Coincidence?!
    Perhaps not.
    The name "Jon D. Moulton (Ph.D.)" is frequently associated with the word "morpholino" (even in Google Scholar).
    According to this study (Kloosterman, W.P. et al., 2007), Jon D. Moulton is connected to Gene Tools, Philomath, Oregon.
    LOL...there is this thing called 'profile page', Tab-About Me...

    About Jon Moulton

    LocationCorvallis, Oregon, USA Interestscamping, bicycling, music, China
    Occupation - Scientist with Gene Tools, LLC.
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    Quote Originally Posted by scheherazade View Post
    Quote Originally Posted by blackscorp View Post

    I meant directly from pc... without need for upload to other site
    You can upload to your own album at your profile page on this site and then link to it. I don't know about direct from your own computer otherwise.
    I can give a try...
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  24. #23  
    Forum Masters Degree mat5592's Avatar
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    Quote Originally Posted by scheherazade View Post
    Quote Originally Posted by Cogito Ergo Sum View Post
    Quote Originally Posted by mat5592 View Post
    In addition, his location is Corvallis, Oregon, the location of Oregon State University, where this particular study was published.

    Coincidence?!
    Perhaps not.
    The name "Jon D. Moulton (Ph.D.)" is frequently associated with the word "morpholino" (even in Google Scholar).
    According to this study (Kloosterman, W.P. et al., 2007), Jon D. Moulton is connected to Gene Tools, Philomath, Oregon.
    LOL...there is this thing called 'profile page', Tab-About Me...

    About Jon Moulton

    LocationCorvallis, Oregon, USA Interestscamping, bicycling, music, China
    Occupation - Scientist with Gene Tools, LLC.
    That probably should have been our first step
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  25. #24  
    Forum Masters Degree mat5592's Avatar
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    Quote Originally Posted by Jon Moulton View Post
    I did enter Gene Tools in my profile. I've been working with Morpholino antisense for almost 14 years now. My wife Hong invented the Morpholino-peptide conjugates at Sarepta Therapeutics (it was named AVI BioPharma back then); she's at Oregon State University now.

    We're both still working with Morpholinos. Our daughters suffer the dinner-table conversations.
    Sounds like enjoyable dinner-talk to me!
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  26. #25  
    Moderator Moderator Cogito Ergo Sum's Avatar
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    Quote Originally Posted by scheherazade View Post
    LOL...there is this thing called 'profile page', Tab-About Me...

    Too obvious!

    Quote Originally Posted by Jon Moulton View Post
    I did enter Gene Tools in my profile. I've been working with Morpholino antisense for almost 14 years now. My wife Hong invented the Morpholino-peptide conjugates at Sarepta Therapeutics (it was named AVI BioPharma back then); she's at Oregon State University now.

    We're both still working with Morpholinos. Our daughters suffer the dinner-table conversations.

    Interesting! I have not exactly looked into all the details of morpholinos (I did not want to overload my OP with too much research papers), but it is certainly worth further investigation. May I ask you how you found this site and this particular thread? Was it by accident or were you a regular guest?
    "The only safe rule is to dispute only with those of your acquaintance of whom you know that they possess sufficient intelligence and self-respect not to advance absurdities; to appeal to reason and not to authority, and to listen to reason and yield to it; and, finally, to be willing to accept reason even from an opponent, and to be just enough to bear being proved to be in the wrong."

    ~ Arthur Schopenhauer, The Art of Being Right: 38 Ways to Win an Argument (1831), Stratagem XXXVIII.
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    Making antisense Jon Moulton's Avatar
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    Interesting! I have not exactly looked into all the details of morpholinos (I did not want to overload my OP with too much research papers), but it is certainly worth further investigation. May I ask you how you found this site and this particular thread? Was it by accident or were you a regular guest?
    I Google Morpholino and related keywords daily to track down new publications, which I enter into a publication database (pubs.gene-tools.com). The original post in this thread was returned by the Google search, so I created a profile here to join the conversation.
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    Northern Horse Whisperer Moderator scheherazade's Avatar
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    Quote Originally Posted by Jon Moulton View Post
    Interesting! I have not exactly looked into all the details of morpholinos (I did not want to overload my OP with too much research papers), but it is certainly worth further investigation. May I ask you how you found this site and this particular thread? Was it by accident or were you a regular guest?
    I Google Morpholino and related keywords daily to track down new publications, which I enter into a publication database (pubs.gene-tools.com). The original post in this thread was returned by the Google search, so I created a profile here to join the conversation.
    An excellent strategy.

    Those web-bots are getting devilishly efficient and very often a new OP will be on the front page of a search within minutes of it's posting, a fact which I first observed about a year or so ago.
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