Inducible production of erythropoietin using intramuscular injection of block copolymer/DNA formulation

Richard, Peggy; Pollard, H.; Lanctin, Caroline; Bello-Roufai, Mahajoub; Désigaux, Léa; Escande, Denis; Pitard, Bruno

doi:10.1002/jgm.631

Cited by 28 publications

(18 citation statements)

References 28 publications

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“…Second, when a long term monitoring study of miRNA expression has to be performed, RILES has a restricted application to immunodeficient mice. Although we did not demonstrate the presence of an immunological response developed against the prokaryotic origin of the CymR repressor molecule, it is likely that CymR is immunogenic in immunocompetent mice as already demonstrated with other prokaryotic-inducible expression systems (52,53). The use of transgenic animals bearing RILES in their genomes might overcome this limitation and will provide, in the meantime, a reliable tool to monitor the expression of miRNAs during embryonic development.…”

Section: Discussioncontrasting

confidence: 52%

RILES, a novel method for temporal analysis of the in vivo regulation of miRNA expression

Ezzine

Vassaux

Pitard

et al. 2013

Nucleic Acids Research

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Novel methods are required to investigate the complexity of microRNA (miRNA) biology and particularly their dynamic regulation under physiopathological conditions. Herein, a novel plasmid-based RNAi-Inducible Luciferase Expression System (RILES) was engineered to monitor the activity of endogenous RNAi machinery. When RILES is transfected in a target cell, the miRNA of interest suppresses the expression of a transcriptional repressor and consequently switch-ON the expression of the luciferase reporter gene. Hence, miRNA expression in cells is signed by the emission of bioluminescence signals that can be monitored using standard bioluminescence equipment. We validated this approach by monitoring in mice the expression of myomiRs-133, −206 and −1 in skeletal muscles and miRNA-122 in liver. Bioluminescence experiments demonstrated robust qualitative and quantitative data that correlate with the miRNA expression pattern detected by quantitative RT-PCR (qPCR). We further demonstrated that the regulation of miRNA-206 expression during the development of muscular atrophy is individual-dependent, time-regulated and more complex than the information generated by qPCR. As RILES is simple and versatile, we believe that this methodology will contribute to a better understanding of miRNA biology and could serve as a rationale for the development of a novel generation of regulatable gene expression systems with potential therapeutic applications.

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Section: Discussioncontrasting

confidence: 52%

RILES, a novel method for temporal analysis of the in vivo regulation of miRNA expression

Ezzine

Vassaux

Pitard

et al. 2013

Nucleic Acids Research

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“…These observations prompted researchers to explore and define new breakthrough approaches for in vivo gene transfer. In this context, others polymers displaying few or no charges have been recently developed and appear very promising to transfect efficiently and safely various organs in vivo after loco-regional administration in muscle and heart [52][53][54][55][56][57], lung [58] and eyes [59]. These block polymers consisting of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) exhibit amphiphilic properties in aqueous solutions, because PPO homopolymer phase-separates from water at relative low temperature, whereas POE is well soluble in water.…”

Section: New Classes Of Vectors Promote High Gene Transfer In Vivomentioning

confidence: 99%

Physicochemical Parameters of Non-Viral Vectors that Govern Transfection Efficiency

Barteau¹,

Chèvre²,

Letrou-Bonneval³

et al. 2008

CGT

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Gene therapy is based on the vectorization of nucleic acids to target cells and their subsequent expression. Cationic lipids and polymers are the most widely used vectors for the delivery of DNA into cultured cells. Nowadays, numerous reagents made of these cationic molecules are commercially available and used by researchers from the academic and industrial field. By contrast their evaluations in preclinical programs have revealed that their use for in vivo applications will be more problematic than their massive use in vitro. This is mostly due to the physicochemical properties of cationic vectors/DNA complexes, which are the result of their mode of interaction. Indeed, these cationic vectors interact through electrostatic forces with negatively charged DNA. This results in the formation of highly organized positively charged supramolecular structures where DNA molecules are condensed. Association of DNA with cationic lipids under a micellar or liposomal form leads to lamellar organization with DNA molecules sandwiched between lipid bilayers. Although the lamellar phase is the common described structure, as evidenced by small-angle X-ray scattering and electron microscopy, some cationic lipid combined with a hexagonal forming lipid could also result with DNA in an inverted hexagonal structure. Despite a lot of effort, the precise mechanism of gene transfer with cationic vector is still ill-defined. Here, our objective was to overview the main relationships between the physico chemical properties of cationic lipid/DNA complexes and their transfection efficiency. An overview of a new class of vectors consisting of amphiphilic block copolymers designed for in vivo delivery is also presented and discussed.

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“…Efficient systemic secretion of hepatocyte growth factor following intramuscular injection of plasmid complexed with SP1017 and electroporation has been confirmed in rats [Riera et al, 2004]. An increase in erythropoietin secretion and haematocrit following intramuscular delivery of an erythropoietin plasmid formulated with PE6400 has been demonstrated in mice [Richard et al, 2005].…”

Section: Co-administration Of Other Agents To Enhance Gene Transfermentioning

confidence: 96%

“…Antibodies against the tetracycline transactivator were detected in mice injected with plasmid encoding this in combination with an erythropoietin gene [Richard et al, 2005]. In a nonhuman primate study, intramuscular injection of a plasmid vector encoding the tetracycline transactivator resulted in cellular and humoral immune response to the transcription factor and reduced duration of reporter gene expression [Latta-Mahieu et al, 2002].…”

Section: Immune Response To Transactivatormentioning

confidence: 98%

Plasmid-Mediated Muscle-Targeted Gene Therapy for Circulating Therapeutic Protein Replacement: A Tale of the Tortoise and the Hare?

Ratanamart¹,

Shaw²

2006

CGT

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There is now conclusive evidence that gene therapy can lead to real clinical benefit. Initial enthusiasm has been muted by set-backs related to viral vectors including retroviral oncogenesis and adenoviral inflammatory response. Plasmid-mediated muscle-targeted gene transfer offers the potential of a cost-effective pharmaceutical grade therapy delivered by simple intramuscular injection without the need for anaesthetic, cell culture, transplantation or immunosuppression. This approach is particularly appropriate for long-term circulating therapeutic protein replacement currently requiring repeated injection therapy. Wide-ranging clinical applications include haemophilia, chronic anaemia, growth hormone deficiency and diabetes. Inadequate transgene expression, unregulated protein delivery and immune response have been major limiting factors. Recent innovations including in situ electroporation enabling sustained systemic protein delivery within the therapeutic range are reviewed. Pharmacological and physiological approaches to regulation are discussed in addition to the role of innate and humoral immunity. Translation of advances in all of these areas to clinical success will enable muscle-targeted gene therapy to capitalise on its inherent strengths and realise its long-standing promise.

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Inducible production of erythropoietin using intramuscular injection of block copolymer/DNA formulation

Abstract: Intramuscular injection of plasmid DNA formulated with PE6400 provides an efficient and simple method for secretion and production of non-muscle proteins.

Cited by 28 publications

References 28 publications

RILES, a novel method for temporal analysis of the in vivo regulation of miRNA expression

RILES, a novel method for temporal analysis of the in vivo regulation of miRNA expression

Physicochemical Parameters of Non-Viral Vectors that Govern Transfection Efficiency

Plasmid-Mediated Muscle-Targeted Gene Therapy for Circulating Therapeutic Protein Replacement: A Tale of the Tortoise and the Hare?

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