Radiolabelled Oligonucleotides for Imaging of Gene Expression with PET

Lendvai, Gábor; Estrada, Sergio; Bergström, Mats

doi:10.2174/092986709789712844

Cited by 28 publications

(21 citation statements)

References 140 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, real-time imaging of transcription in living cells can capture the act of transcription including the kinetics of RNA polymerase movement, the association of transcription factors, and the progression of the polymerase on the gene. Some promising approaches use nanoparticles [80] or antisense oligonucleotides, such as those labeled with radionuclides [81] or so-called molecular beacons, unimolecular stem-loop structures that very efficiently couple target recognition with specific fluorescent signals [82]. These strategies can even be coupled with existing imaging modalities such as positron emission tomography or MRI to noninvasively image cerebral RNAs in live animals [81, 83].…”

Section: Methods and Technologies For Epigenetics And Epigenomicsmentioning

confidence: 99%

Advances in Epigenetics and Epigenomics for Neurodegenerative Diseases

Qureshi

Mehler

2011

Curr Neurol Neurosci Rep

View full text Add to dashboard Cite

In the post-genomic era, epigenetic factors—literally those that are “over” or “above” genetic ones and responsible for controlling the expression and function of genes—have emerged as important mediators of development and aging; gene-gene and gene-environmental interactions; and the pathophysiology of complex disease states. Here, we provide a brief overview of the major epigenetic mechanisms (ie, DNA methylation, histone modifications and chromatin remodeling, and non-coding RNA regulation). We highlight the nearly ubiquitous profiles of epigenetic dysregulation that have been found in Alzheimer’s and other neurodegenerative diseases. We also review innovative methods and technologies that enable the characterization of individual epigenetic modifications and more widespread epigenomic states at high resolution. We conclude that, together with complementary genetic, genomic, and related approaches, interrogating epigenetic and epigenomic profiles in neurodegenerative diseases represent important and increasingly practical strategies for advancing our understanding of and the diagnosis and treatment of these disorders.

show abstract

Section: Methods and Technologies For Epigenetics And Epigenomicsmentioning

confidence: 99%

Advances in Epigenetics and Epigenomics for Neurodegenerative Diseases

Qureshi

Mehler

2011

Curr Neurol Neurosci Rep

View full text Add to dashboard Cite

show abstract

“…There are two approaches to image the expression of TGs with PET: 1) If a specific PET probe is available, the mRNA or protein encoded by the TG can be detected directly (Figure 4). 36,67 2) If a specific PET probe is not available, the TG can be imaged indirectly by linking its expression to the expression of a PET IRG. The direct approach can be used to monitor expression of HSV1-tk or its mutant HSV1-sr39tk during suicide gene therapy of cancer (Figure 5), since several specific PET probes are available for detecting the enzymes encoded by these TGs/PET IRGs 13,14,25,36,68-71.…”

Section: Imaging Therapeutic Transgenesmentioning

confidence: 99%

Positron Emission Tomography Reporter Genes and Reporter Probes: Gene and Cell Therapy Applications

Yaghoubi¹,

Campbell²,

Radu³

et al. 2012

Theranostics

102

View full text Add to dashboard Cite

Positron emission tomography (PET) imaging reporter genes (IRGs) and PET reporter probes (PRPs) are amongst the most valuable tools for gene and cell therapy. PET IRGs/PRPs can be used to non-invasively monitor all aspects of the kinetics of therapeutic transgenes and cells in all types of living mammals. This technology is generalizable and can allow long-term kinetics monitoring. In gene therapy, PET IRGs/PRPs can be used for whole-body imaging of therapeutic transgene expression, monitoring variations in the magnitude of transgene expression over time. In cell or cellular gene therapy, PET IRGs/PRPs can be used for whole-body monitoring of therapeutic cell locations, quantity at all locations, survival and proliferation over time and also possibly changes in characteristics or function over time. In this review, we have classified PET IRGs/PRPs into two groups based on the source from which they were derived: human or non-human. This classification addresses the important concern of potential immunogenicity in humans, which is important for expansion of PET IRG imaging in clinical trials. We have then discussed the application of this technology in gene/cell therapy and described its use in these fields, including a summary of using PET IRGs/PRPs in gene and cell therapy clinical trials. This review concludes with a discussion of the future direction of PET IRGs/PRPs and recommends cell and gene therapists collaborate with molecular imaging experts early in their investigations to choose a PET IRG/PRP system suitable for progression into clinical trials.

show abstract

“…Additionally, PNAs are able to invade regions of secondary structure in the target mRNA, and the resulting PNA·RNA complexes are resistant to the action of RNase H which would otherwise degrade the mRNA and result in a loss of signal. While there are several reports on the use of PNAs to both inhibit 19 and image gene expression 20–24 , application of PNAs as regulators and imaging agents of gene expression in vivo has been hampered by their poor cellular uptake and rapid clearance 15, 25, 26 . To overcome the permeability problems, PNAs have been conjugated to a variety of cell penetrating peptides and other ligands, which have been shown to improve their uptake in cell culture through endocytosis though they often remain trapped in endosomes 27, 28 .…”

Section: Introductionmentioning

confidence: 99%

Dual Peptide Nucleic Acid- and Peptide-Functionalized Shell Cross-Linked Nanoparticles Designed to Target mRNA toward the Diagnosis and Treatment of Acute Lung Injury

et al. 2012

View full text Add to dashboard Cite

In this work, multi-functional bio-synthetic hybrid nanostructures were prepared and studied for their potential utility in the recognition and inhibition of mRNA sequences for inducible nitric oxide synthase (iNOS), which are overexpressed at sites of inflammation, such as in cases of acute lung injury. Shell crosslinked knedel-like polymer nanoparticles (SCKs) that present peptide nucleic acids, for binding to complementary mRNAs, and cell penetrating peptides (CPPs), to gain cell entry, along with fluorescent labels and sites for radiolabeling, were prepared by a series of robust, efficient and versatile synthetic steps that proceeded from monomers to polymers to functional nanoparticles. Amphiphilic block graft copolymers having combinations of methoxy- and thioacetyl-terminated poly(ethylene glycol) (PEG) and DOTA-lysine units grafted from the backbone of poly(acrylic acid) (PAA) and extending with a backbone segment of poly(octadecyl acrylate-co-decyl acrylate) (P(ODA-co-DA)) were prepared by a combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and chemical modification reactions, which were then used as the building blocks for the formation of well-defined SCKs decorated with reactive thiols accessible to the surface. Fluorescent labeling with Alexa Fluor 633 hydrazide was then accomplished by amidation with residual acrylic acid residues within the SCK shells. Finally, the PNAs and CPP units were covalently conjugated to the SCKs via Michael addition of thiols on the SCKs to maleimide units on the termini of PNAs and CPPs. Confirmation of the ability of the PNAs to bind selectively to the target iNOS mRNAs when tethered to the SCK nanoparticles was determined by in vitro competition experiments. When attached to the SCKs having a hydrodynamic diameter of 60 ± 16 nm, the Kd values of the PNAs were ca. an order of magnitude greater than the free PNAs, while the mismatched PNA showed no significant binding.

show abstract

Radiolabelled Oligonucleotides for Imaging of Gene Expression with PET

Cited by 28 publications

References 140 publications

Advances in Epigenetics and Epigenomics for Neurodegenerative Diseases

Advances in Epigenetics and Epigenomics for Neurodegenerative Diseases

Positron Emission Tomography Reporter Genes and Reporter Probes: Gene and Cell Therapy Applications

Dual Peptide Nucleic Acid- and Peptide-Functionalized Shell Cross-Linked Nanoparticles Designed to Target mRNA toward the Diagnosis and Treatment of Acute Lung Injury

Contact Info

Product

Resources

About