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Rog Yocum

Hi Merry, Elio,
I don't have many opportunities to read your fascinating blogs, but I caught the one on injection of phage DNA. You raised an issue that I never thought of: how DOES 50 microns of stiff dsDNA get crammed inside the head? It must be kinked or supercoiled or bacto-histoned or something. Perhaps the thermodynamic urge to simply straighten out could propel the injection. I would be interested in your comments, as you have thought much more about this than I, and are much more knowledgable. Thanks -Rog Yocum

Merry replies: Ron, your comment targets some key issues in DNA packaging and delivery. Stuffing that much DNA, against its will into a phage head takes work, an efficient packaging motor, and a compact configuration for the pkgd DNA. Here's a link to one paper about one particular motor:

http://www.nature.com/nature/journal/v408/n6813/full/408745a0.html?free=2

and a recent paper concerning the toroidal DNA configuration inside the capsid:

http://www.cell.com/biophysj/abstract/S0006-3495%2811%2900322-5

It would seem elegantly phage-like to use the pent-up force of the encapsidated DNA to propel the DNA into the host cell during infection, but there are serious problems with that model, some of which I mentioned in the post itself. That's why I featured the alternative model where the forces involved are osmotic/hydrostatic.

The whole packaging and delivery business is impressive to all of us, likely more so to one such as yourself who is aware of the challenges in the development of "biotechnology" for human use.


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