tag:blogger.com,1999:blog-10781944.post9121187851825680098..comments2024-03-28T00:36:36.460-07:00Comments on The Tree of Life: The story behind “Programmable removal of bacterial strains by use of genome-targeting CRISPR-Cas systems”Jonathan Eisenhttp://www.blogger.com/profile/07953790938128734305noreply@blogger.comBlogger2125tag:blogger.com,1999:blog-10781944.post-24327620812733587722014-02-17T17:53:42.122-08:002014-02-17T17:53:42.122-08:00Ben, thanks for pointing out these examples! I was...Ben, thanks for pointing out these examples! I was not familiar with Avidbiotics, which are now firmly in my radar. I really like the idea of fusing bacteriophage tail fibers to the pyocins for targeted killing. It requires finding an appropriate bacteriophage, although it gets around our major challenge of getting something into the cell.<br /><br />I can understand clinicians' hesitance about narrow spectrum, targeted infection management. However, with further instances of multi drug resistance, the growing importance of beneficial bacteria, and the decreasing cost of sequencing technologies, I can only imagine that targeted therapeutics may be become a reality in time. Certainly, my group's work has a ways to go before it could reach any application--industrial or medical. At the very least, I think it fuels further conversations about the importance of narrow-spectrum drugs and breaks us from the status quo.Anonymoushttps://www.blogger.com/profile/10175363401917072459noreply@blogger.comtag:blogger.com,1999:blog-10781944.post-3551062164217623442014-02-17T07:06:40.723-08:002014-02-17T07:06:40.723-08:00From my perspective, there are a series of technol...From my perspective, there are a series of technologies and approaches which intermingle to create possibilities for narrow spectrum - very narrow spectrum - identification, construction, removal. All of this can enable a sniper/smart bomb approach to managing the microbiome, which is required for any sort of counter insurgency - in contrast to managing an epidemic/invasion. <br /><br />I would like to highlight a couple here. First, since this is Chase's forum, I should refer to his CRISPR approach for bacterial removal. Then, I should add the Avidbiotics, which has another method of targeted strain removal. It also can produce a method for diagnostic identification. Third, Advandx with FDA approved diagnostic PNA-FISH, and the possibility of grafting Borisey's CLASI (or its descendants) onto the probes. There are also people working with bacteriocins, including those at Natick (Mello and Stote). Finally, the combinatorial approach from the Sanger (Lawley et al, with Parkhill), which is more about composing and testing than targeting.<br /><br />Many people - particularly clinicians - have said negative things about the realism of narrow spectrum, targeted infection management. There are some big issues with the cost, testing, and approval for antibiotics such that designing small molecules against specific strains is quite impractical; not to mention the problem with diagnostics, making a closed loop - no new diagnostics because no appropriate therapeutics (nothing to do with the information), no new therapies because of no appropriate diagnostics.<br /><br />Chase's work erodes some of that internal consistency. It also has obvious industrial applications (fermentations) such that there may be a way to build on it outside of the FDA approval process, or in a food, rather than drug, regulatory process. I encourage everyone to take a bold vision of what can be, but not to oversell what is already accomplished.BenKhttps://www.blogger.com/profile/16784998250207335412noreply@blogger.com