New therapeutic targets in immune disorders: ItpkB, Orai1 and UNC93B.
BACKGROUND
Sequencing of the murine and human genomes has enabled large-scale functional genomics approaches to target identification. This holds the promise of drastically accelerating target discovery. Moreover, by providing an initial validation coincident with target identification, cell based cDNA or small interfering RNA (siRNA) screens and in particular genome-wide in vivo approaches, including forward or reverse genetics and analyses of natural gene polymorphisms, can move the relatively late step of target validation to the beginning of the process, reducing the risk of pursuing targets with little in vivo relevance.


OBJECTIVE
We critically discuss the value of combining functional genomics with traditional approaches for accelerating target identification and validation.


METHODS
We evaluate the potentials of inositol (1,4,5)trisphosphate 3-kinase B (ItpkB), Orai1 and UNC93B, three particularly interesting proteins that were recently identified through functional genomics, as targets in immune disorders.


CONCLUSIONS
Combining functional genomics with traditional approaches can accelerate target discovery and validation, but requires a follow-up platform that integrates and analyzes all relevant data for assessment of the clinical potential of the growing number of novel targets.
Huang
Yina H
YH
The Scripps Research Institute, Department of Immunology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Hoebe
Kasper
K
Sauer
Karsten
K
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D023281:Genomics; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D026901:Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D000071740:ORAI1 Protein; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000187:drug effects* / Q000378:metabolism
D015220:Calcium Channels; D026901:Membrane Transport Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C454130:UNC93B1 protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase