Loanalone - While on the surface Ariad and Sangamo may appear to addressing similar targets with parallel technologies, the two approaches are quite different.
In a nutshell, Sangamo targets the modification of activity of endogenous genes by altering the zinc-finger transcription factor binding activity. Thus let's say the insulin gene has a ZFP site in its promoter which is critical for activation of the gene. SGMO might design a ZFP that can specifically interact with the insulin promoter, supplanting and/or enhancing the normal levels of the insulin-promoter-specific ZFP, thereby potentially raising the insulin titer.
In contrast Ariad's ARGENT and RAPID systems do not interact with endogenous promoters but rely on their own 'manufacturing plant' to deliver a compound. With ARGENT, for example, a set of vectors (adeno-associated virus containing specific genes) are delivered to a cell. The genes inserted into the vectors fall into two categories: 1. A construct containing a promoter upstream of a gene whose protein product is the drug to be delivered. This construct is inactive unless stimulated; 2. Constructs containing promoter-activator genes. These constructs are continuously expressed. The promoter-activator genes, whose protein products exist in the cell at all times, do not bind to the 'drug-construct' promoter due to the requirements of proximity and orientation on the promoter which does not occur randomly. However, when a 'dimerizer' is given to the cell, the promoter activator proteins ARE brought into the proper alignment, they bind to the promoter, activate the gene, and the protein is expressed. This entire scenario can be applied to the insulin example: deliver a drug construct containing the insulin gene (usually placed in muscle cells) together with the promoter activator genes. When insulin demand becomes manifest, apply the dimerizer (a pill, orally), and insulin levels will rise. Ariad has successfully achieved this mice.
Thus Sangamo 'designs' compounds to activate 'endogenous' promoters while Ariad applies a completely artificial system using 'exogenous' constructs to deliver drugs.
The question whether these two approaches represent different platforms is, IMO, unanswerable and mostly likely, not critical. I cannot state with certainty whether one approach outflanks another for certain diseases or under certain circumstances. I cannot state for certain as well whether, in the end, the more successful methodology will be the result of better marketing, more cash, etc. on the one hand, or better fundamental science on the other. One can only hope the latter prevails.
I hope this helps. |
