Image-guided, noninvasive, spatiotemporal control of gene expression

Deckers, Roel; Quesson, Bruno; Arsaut, Josette; Eimer, Sandrine; Couillaud, Franck; Moonen, Chrit

doi:10.1073/pnas.0806936106

Cited by 78 publications

(66 citation statements)

References 22 publications

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“…Future studies will focus on fine-tuning regenerative factor release kinetics and localization by precisely controlling thermal dose and spatial localization. This can be achieved using focused ultrasound heating, a technology that can be combined with magnetic resonance temperature imaging to guide the deposition of thermal energy and gene activation (Deckers et al, 2009). The gene expression system we developed holds much promise for applications where the temporal and spatial control of VEGF delivery is desired such as in ischemia or applications where a vascular bed is needed for tissue regeneration.…”

Section: Discussionmentioning

confidence: 99%

“…Heating can be achieved by a variety of methods, such as direct application of a localized thermal stimulus or by using high-intensity ultrasound, which can be focused to small volumes. The human HSP70B promoter, which exhibits extremely low basal activity and high heat inducibility (Dreano et al, 1986), has been successfully used to target several transgenes in vivo (Braiden et al, 2000;Vekris et al, 2000;Smith et al, 2002;Deckers et al, 2009). However, because it is susceptible to thermal activation associated with local inflammation or fever, it does not provide the necessary stringency for gene therapy applications.…”

Section: Introductionmentioning

confidence: 99%

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Spatiotemporal Control of Vascular Endothelial Growth Factor Expression Using a Heat-Shock-Activated, Rapamycin-Dependent Gene Switch

Martín-Saavedra

Wilson

Voellmy

et al. 2013

Human Gene Therapy Methods

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A major challenge in regenerative medicine is to develop methods for delivering growth and differentiation factors in specific spatial and temporal patterns, thereby mimicking the natural processes of development and tissue repair. Heat shock (HS)-inducible gene expression systems can respond to spatial information provided by localized heating, but are by themselves incapable of sustained expression. Conversely, gene switches activated by small molecules provide tight temporal control and sustained expression, but lack mechanisms for spatial targeting. Here we combine the advantages of HS and ligand-activated systems by developing a novel rapamycin-regulated, HS-inducible gene switch that provides spatial and temporal control and sustained expression of transgenes such as firefly luciferase and vascular endothelial growth factor (VEGF). This gene circuit exhibits very low background in the uninduced state and can be repeatedly activated up to 1 month. Furthermore, dual regulation of VEGF induction in vivo is shown to stimulate localized vascularization, thereby providing a route for temporal and spatial control of angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Spatiotemporal Control of Vascular Endothelial Growth Factor Expression Using a Heat-Shock-Activated, Rapamycin-Dependent Gene Switch

Martín-Saavedra

Wilson

Voellmy

et al. 2013

Human Gene Therapy Methods

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“…Thermometric information can then be used for adaptive ablation strategies, which employ feedback control of the HIFU power and dynamic modifications of the HIFU trajectory [7]: Since a complete destruction of the tumor is required to assure therapeutic success, efficient ablation control strategies are required exploiting both electronic beam steering and mechanical displacements of the HIFU transducer. The feedback control algorithm can either be based on the targeted temperature, as it is required for the use of HIFU in local drug delivery applications [8], or directly on necrosis estimates as is preferable for the direct thermal destruction of tumors [6].…”

Section: Introductionmentioning

confidence: 99%

Extended Kalman Filtering for Continuous Volumetric MR-Temperature Imaging

Senneville

Roujol

Hey

et al. 2013

IEEE Trans. Med. Imaging

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Real time magnetic resonance (MR) thermometry has evolved into the method of choice for the guidance of high-intensity focused ultrasound (HIFU) interventions. For this role, MR-thermometry should preferably have a high temporal and spatial resolution and allow observing the temperature over the entire targeted area and its vicinity with a high accuracy. In addition, the precision of real time MR-thermometry for therapy guidance is generally limited by the available signal-to-noise ratio (SNR) and the influence of physiological noise. MR-guided HIFU would benefit of the large coverage volumetric temperature maps, including characterization of volumetric heating trajectories as well as near- and far-field heating. In this paper, continuous volumetric MR-temperature monitoring was obtained as follows. The targeted area was continuously scanned during the heating process by a multi-slice sequence. Measured data and a priori knowledge of 3-D data derived from a forecast based on a physical model were combined using an extended Kalman filter (EKF). The proposed reconstruction improved the temperature measurement resolution and precision while maintaining guaranteed output accuracy. The method was evaluated experimentally ex vivo on a phantom, and in vivo on a porcine kidney, using HIFU heating. On the in vivo experiment, it allowed the reconstruction from a spatio-temporally under-sampled data set (with an update rate for each voxel of 1.143 s) to a 3-D dataset covering a field of view of 142.5×285×54 mm(3) with a voxel size of 3×3×6 mm(3) and a temporal resolution of 0.127 s. The method also provided noise reduction, while having a minimal impact on accuracy and latency.

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“…Their application to adenoviral vectors is intended to shield from immune responses, similar to approaches published by others (32) . The consortium will construct vectors having the cDNAs of interest (IL-10, TGF β and BMP-2) under the controls of inducible promoters [Cox-2 responding to an infl ammatory environment (33) , Hsp70 responding to heat (34) , tet system responding to doxycycline (35) ]. Vector pairs encoding different factors will be embedded in different phases of the composite matrix (e.g., BMP-2 on MBCP/TGF β 1 in polymer hydrogel) yielding a system with multiple levels of spatiotemporal bioactivity control for cells colonising the matrix.…”

Section: The Gene Vectorsmentioning

confidence: 99%

Gene activated matrices for bone and cartilage regeneration in arthritis

Plank

Eglin

Fahy

et al. 2012

European Journal of Nanomedicine

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The GAMBA Consortium is developing a novel gene-activated matrix platform for bone and cartilage repair with a focus on osteoarthritis-related tissue damage. The scientifi c and technological objectives of this project are complemented with an innovative program of public outreach, actively linking patients and society to the evolvement of this project. The GAMBA platform will implement a concept of spatiotemporal control of regenerative bioactivity on command and demand.

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Image-guided, noninvasive, spatiotemporal control of gene expression

Cited by 78 publications

References 22 publications

Spatiotemporal Control of Vascular Endothelial Growth Factor Expression Using a Heat-Shock-Activated, Rapamycin-Dependent Gene Switch

Spatiotemporal Control of Vascular Endothelial Growth Factor Expression Using a Heat-Shock-Activated, Rapamycin-Dependent Gene Switch

Extended Kalman Filtering for Continuous Volumetric MR-Temperature Imaging

Gene activated matrices for bone and cartilage regeneration in arthritis

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