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SMaRTTM Image
SMaRTTM Image can be used to perform real time molecular imaging of gene expression and has potential applications both in pre-clinical research and human diagnostics. SMaRTTM has the ability to trans-splice any reporter gene into essentially any expressed pre-mRNA that contains introns. Reporter genes that encode fluorescent or luminescent proteins may be used for optical imaging; other reporters such as thymidine kinase make the technology adaptable to positron emission tomography (PET). In pre-clinical research, imaging can be applied in target validation, drug discovery or drug and vector distribution. Advantages: SMaRTTM Image offers several advantages over conventional imaging methods. Current approaches to imaging gene expression include both indirect and direct methods. In the most common approach to indirect imaging, an approximation of the promoter that regulates a gene of interest is used to drive expression of a reporter gene. This approach may not accurately mimic endogenous regulation and requires prior knowledge of the DNA sequence that comprises the transcriptional control elements for the gene. This information is often unavailable or has to be obtained for each new gene of interest. In contrast, the development of PTMs for SMaRTTM Image only requires knowledge of a target intron sequence. This information is readily available from the sequence of the human genome and can be used to rapidly produce PTMs for any new target gene.
Direct approaches to molecular imaging traditionally employ molecules such as antibodies that interact with the gene product of interest. Screening for new molecules is labor intensive and reduces the rate at which new imaging reagents can be developed. SMaRTTM allows for the rapid development of new imaging molecules. The PTMs used for molecular imaging will have two standard coding sequences, that of a fluorescent/luminescent or PET reporter, and will differ only in the binding domain which is specific for each target pre-mRNA. This modular nature of the PTM is a distinct advantage of SMaRTTM Image.
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