Molecular imaging of gene expression in living subjects by spliceosome-mediated RNA trans-splicing.
Spliceosome-mediated RNA trans-splicing (SMaRT) provides an effective means to reprogram mRNAs and the proteins they encode. SMaRT technology has a broad range of applications, including RNA repair and molecular imaging, each governed by the nature of the sequences delivered by the pre-trans-splicing molecule. Here, we show the ability of SMaRT to optically image the expression of an exogenous gene at the level of pre-mRNA splicing in cells and living animals. Because of the modular design of pre-trans-splicing molecules, there is great potential to employ SMaRT to image the expression of any arbitrary gene of interest in living subjects. In this report, we describe a model system that demonstrates the feasibility of imaging gene expression by transsplicing in small animals. This represents a previously undescribed approach to molecular imaging of mRNA levels in living subjects.
Bhaumik
S
S
Department of Radiology and Bio-X Program, Stanford University, James H. Clark Center E150, 318 Campus Drive, Stanford, CA 94305-5427, USA.
Walls
Z
Z
Puttaraju
M
M
Mitchell
L G
LG
Gambhir
S S
SS
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D008163:Luminescent Measurements; D051379:Mice; D008819:Mice, Nude; D055095:Optics and Photonics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017381:Spliceosomes / Q000235:genetics* / Q000378:metabolism*
D017931:DNA Primers; D012333:RNA, Messenger