Will “Target Protector” Technology Come In Play?

Last month, the Schier lab from Harvard extended their impressive work on the function of microRNAs in the zebrafish model of development (Choi et al.: “Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430”. Science 318: 271).

Antisense oligos to microRNAs are one method to experimentally infer microRNA function through loss-of-function analysis. However, this method becomes problematic when the intention is to study the biology of a particular microRNA-target interaction given the multitude of predicted targets for a given microRNA, typically estimated to be around a hundred per microRNA.

In order to overcome this problem, the investigators designed morpholino antisense oligos (morpholinos are quite popular with the fish community), which they termed “Target Protectors”. These are supposed to hybridise to a defined microRNA target site thereby blocking the function of the microRNA acting on that particular target site. This actually turned out to work quite well in the zebrafish and future publications should demonstrate the versatility of this new methodology.

The reason why I suddenly blog about it is because I had the pleasure today to listen to a presentation by Dr. Alex Schier in which it became apparent to me that there may be investor interest in commercializing the technology. This would complement the microRNA antagonist (“antagomirs”) approach currently pursued by the likes of Regulus, Rosetta Genomics, and Santaris, that aim at therapeutically blocking the microRNA. Given the many targets of a given microRNA, blocking them for therapy is therefore based on the belief that evolutionary pressure should have ensured that their targets are tied to a common biologic phenotype. Target Protectors, on the other hand, may be more specific in upregulating only one transcript that when de-repressed should be therapeutically beneficial. As such, one could imagine targeting the miR-122 target site of HCV, thereby avoiding potential side-effects due to inhibiting the most abundant microRNA in the liver.

It will be interesting to see who will take an interest in this emerging IP estate. It is also notable in this context that Rosetta Genomics, the microRNA target company, has previously mentioned their foresight to patent not only their discovered microRNAs, but also predicted microRNA target sites.

Update (23 November 2007): It has come to my attention that Target Protector has come into play indeed: http://www.stealthbiotech.com/index.asp