Cytogenix (fka CYGX)

[thalio]

HAN,

Oligos are double stranded DNA molecules that can do a number of things once inside a cell. Gum up mRNA (antisense), cleave it (DNA enzyme), grab onto the protein made from mRNA instructions (aptemer), and a couple of other little tricks I’m still learning about.

The end result is that the protein product of some gene doesn't get made--the gene is "silenced". This can have therapeutic effects, obviously, if the gene is one that a virus needs to proliferate, or a bacteria needs to replicate, or a cancer cell needs to stay immortal and build a tumor, etc.

But these natural double stranded DNA molecules (the oligos) are delicate. Think of DNA as a ladder (a twisted one, of course). Those two uprights, the parts that aren't the rungs--biologists call those the "backbone." They are in fact chains of sugar (dioxyribose) and phosphate molecules.

The chemical bonds that hold those uprights together aren't very strong. Enzymes in the bloodstream break them down easily.

Remember, oligos are just lengths of a DNA molecule around twenty or so "rungs" worth. So their "backbones" made of these sugar and phosphate molecules--get broken down in the bloodstream. They fall to pieces and are worthless.

That's a real problem if you're trying to get your oligo into a target cell via injection. Of course the oral route is out, because digestive acids and enzymes would be even worse.

Biologists have tried to solve this problem by replacing the sugar/phosphate backbone with stronger "uprights" for the ladder. But this has often caused immune reactions. There is some promise in second and third generation of this approach, but it’s still up in the air

Next there's the concentration problem. You need to get enough oligos into a cell to "mop up" the mRNA (or protein) you're blocking. That's not easy either.

CYGX makes a DNA machine that manufactures the oligos INSIDE the cells themselves--where bloodstream enzymes can't get at them. The DNA "construct" can express oligos as fast or faster than the gene of interest can make the mRNA you're trying to block.

That's what I mean by saying CYGX technology overcomes some of the toughest delivery problems.

1. degradation (by enzymes in the blood)
2. concentration (high enough to be effective within the cell)

Th