Imperial College London

Emeritus ProfessorCharlesCoutelle

Faculty of MedicineNational Heart & Lung Institute

Emeritus Professor
 
 
 
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Contact

 

+44 (0)7906 614 491c.coutelle

 
 
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Location

 

Open SpaceSir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

106 results found

Al-Allaf FA, Abduljaleel Z, Athar M, Taher MM, Khan W, Mehmet H, Colakogullari M, Apostolidou S, Bigger B, Waddington S, Coutelle C, Themis M, Al-Ahdal MN, Al-Mohanna FA, Al-Hassnan ZN, Bouazzaoui Aet al., 2019, Modifying inter-cistronic sequence significantly enhances IRES dependent second gene expression in bicistronic vector: Construction of optimised cassette for gene therapy of familial hypercholesterolemia., Noncoding RNA Res, Vol: 4, Pages: 1-14

Internal ribosome entry site (IRES) sequences have become a valuable tool in the construction of gene transfer and therapeutic vectors for multi-cistronic gene expression from a single mRNA transcript. The optimal conditions for effective use of this sequence to construct a functional expression vector are not precisely defined but it is generally assumed that the internal ribosome entry site dependent expression of the second gene in such as cassette is less efficient than the cap-dependent expression of the first gene. Mainly tailoring inter-cistronic sequence significantly enhances IRES dependent second gene expression in bicistronic vector further in construction of optimised cassette for gene therapy of familial hypercholesterolemia. We tailored the size of the inter-cistronic spacer sequence at the 5' region of the internal ribosome entry site sequence using sequential deletions and demonstrated that the expression of the 3' gene can be significantly increased to similar levels as the cap-dependent expression of the 5' gene. Maximum expression efficiency of the downstream gene was obtained when the spacer is composed of 18-141 base pairs. In this case a single mRNA transcriptional unit containing both the first and the second Cistron was detected. Whilst constructs with spacer sequences of 216 bp or longer generate a single transcriptional unit containing only the first Cistron. This suggests that long spacers may affect transcription termination. When the spacer is 188 bp, both transcripts were produced simultaneously in most transfected cells, while a fraction of them expressed only the first but not the second gene. Expression analyses of vectors containing optimised cassettes clearly confirm that efficiency of gene transfer and biological activity of the expressed transgenic proteins in the transduced cells can be achieved. Furthermore, Computational analysis was carried out by molecular dynamics (MD) simulation to determine the most emerges as viable cont

Journal article

Coutelle C, 2018, An important step on the long path to clinical application of in utero gene therapy., Gene Ther, Vol: 25, Pages: 451-453

Journal article

Condiotti R, Goldenberg D, Giladi H, Schnitzer-Perlman T, Waddington SN, Buckley SMK, Heim D, Cheung W, Themis M, Coutelle C, Simerzin A, Osejindu E, Wege H, Themis M, Galun Eet al., 2014, Transduction of Fetal Mice With a Feline Lentiviral Vector Induces Liver Tumors Which Exhibit an E2F Activation Signature, MOLECULAR THERAPY, Vol: 22, Pages: 59-68, ISSN: 1525-0016

Journal article

Nowrouzi A, Cheung WT, Li T, Zhang X, Arens A, Paruzynski A, Waddington SN, Osejindu E, Reja S, von Kalle C, Wang Y, Al-Allaf F, Gregory L, Themis M, Holder M, Dighe N, Ruthe A, Buckley SMK, Bigger B, Montini E, Thrasher AJ, Andrews R, Roberts TP, Newbold RF, Coutelle C, Schmidt M, Themis Met al., 2013, The Fetal Mouse Is a Sensitive Genotoxicity Model That Exposes Lentiviral-associated Mutagenesis Resulting in Liver Oncogenesis, MOLECULAR THERAPY, Vol: 21, Pages: 324-337, ISSN: 1525-0016

Journal article

Coutelle C, Waddington SN, Themis M, 2012, Monitoring for potential adverse effects of prenatal gene therapy: mouse models for developmental aberrations and inadvertent germ line transmission., Methods Mol Biol, Vol: 891, Pages: 329-340

So far no systematic studies have been conducted to investigate developmental aberrations after prenatal gene transfer in mice. Here, we suggest procedures for such observations to be applied, tested and improved in further in utero gene therapy experiments. They are based on our own experience in husbandry for transgenic human diseases mouse models and breading, rearing, and observing mice after fetal gene transfer as well as on the systematic screens for monitoring of knock-out mutant mouse phenotypes established in international mutagenesis projects (EUMORPHIA and EUMODIC and subsequently the International Mouse Phenotyping Consortium). We also describe here the analysis procedures for detection of germ line mutations based on quantitative PCR (qPCR) by sperm-DNA analysis and breeding studies.

Journal article

Coutelle C, Waddington SN, 2012, The concept of prenatal gene therapy., Methods Mol Biol, Vol: 891, Pages: 1-7

This introductory chapter provides a short review of the ideas and practical approaches that have led to the present and perceived future development of prenatal gene therapy. It summarizes the advantages and the potential adverse effects of this novel preventive and therapeutic approach to the management of prenatal diseases. It also provides guidance to the range of conditions to which prenatal gene therapy may be applied and to the technical approaches, vectors, and societal/ethical considerations for this newly emerging field of Fetal Medicine.

Journal article

Coutelle C, Waddington SN, 2012, Vector systems for prenatal gene therapy: choosing vectors for different applications., Methods Mol Biol, Vol: 891, Pages: 41-53

This chapter gives a comparative review of the different vector systems applied to date in prenatal gene therapy experiments highlighting the need for versatility and choice for application in accordance with the actual aim of the study. It reviews the key characteristics of the four main gene therapy vector systems and gives examples for their successful application in prenatal gene therapy experiments.

Journal article

Coutelle C, Ashcroft R, 2012, Risks, benefits and ethical, legal, and societal considerations for translation of prenatal gene therapy to human application., Methods Mol Biol, Vol: 891, Pages: 371-387

The still experimental nature of prenatal gene therapy carries a certain degree of risk, both for the pregnant mother as well as for the fetus. Some of the risks are procedural hazards already known from more conventional fetal medicine interventions. Others are more specific to gene therapy such as the potential for interference with normal fetal development, the possibility of inadvertent germ line gene transfer, and the danger of oncogenesis. This chapter reviews the potential risks in relation to the expected benefits of prenatal gene therapy. It discusses the scientific, ethical, legal, and social implications of this novel preventive approach to genetic disease and outlines preconditions to be met in preparation for a potential future clinical application.

Journal article

Mehta V, Abi-Nader KN, Carr D, Wallace J, Coutelle C, Waddington SN, Peebles D, David ALet al., 2012, Monitoring for potential adverse effects of prenatal gene therapy: use of large animal models with relevance to human application., Methods Mol Biol, Vol: 891, Pages: 291-328

Safety is an absolute prerequisite for introducing any new therapy, and the need to monitor the consequences of administration of both vector and transgene to the fetus is particularly important. The unique features of fetal development that make it an attractive target for gene therapy, such as its immature immune system and rapidly dividing populations of stem cells, also mean that small perturbations in pregnancy can have significant short- and long-term consequences. Certain features of the viral vectors used, the product of the delivered gene, and sometimes the invasive techniques necessary to deliver the construct to the fetus in utero have the potential to do harm. An important goal of prenatal gene therapy research is to develop clinically relevant techniques that could be applied to cure or ameliorate human disease in utero on large animal models such as sheep or nonhuman primates. Equally important is the use of these models to monitor for potential adverse effects of such interventions. These large animal models provide good representation of individual patient-based investigations. However, analyses that require defined genetic backgrounds, high throughput, defined variability and statistical analyses, e.g. for initial studies on teratogenic and oncogenic effects, are best performed on larger groups of small animals, in particular mice. This chapter gives an overview of the potential adverse effects in relation to prenatal gene therapy and describes the techniques that can be used experimentally in a large animal model to monitor the potential adverse consequences of prenatal gene therapy, with relevance to clinical application. The sheep model is particularly useful to allow serial monitoring of fetal growth and well-being after delivery of prenatal gene therapy. It is also amenable to serially sampling using minimally invasive and clinically relevant techniques such as ultrasound-guided blood sampling. For more invasive long-term monitoring, we describ

Journal article

Bigger BW, Liao A-Y, Sergijenko A, Coutelle Cet al., 2011, Trial and Error: How the Unclonable Human Mitochondrial Genome was Cloned in Yeast, PHARMACEUTICAL RESEARCH, Vol: 28, Pages: 2863-2870, ISSN: 0724-8741

Journal article

Conese M, Ascenzioni F, Boyd AC, Coutelle C, De Fino I, De Smedt S, Rejman J, Rosenecker J, Schindelhauer D, Scholte BJet al., 2011, Gene and cell therapy for cystic fibrosis: from bench to bedside., J Cyst Fibros, Vol: 10 Suppl 2, Pages: S114-S128

Clinical trials in cystic fibrosis (CF) patients established proof-of-principle for transfer of the wild-type cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelial cells. However, the limited efficacy of gene transfer vectors as well as extra- and intracellular barriers have prevented the development of a gene therapy-based treatment for CF. Here, we review the use of new viral and nonviral gene therapy vectors, as well as human artificial chromosomes, to overcome barriers to successful CFTR expression. Pre-clinical studies will surely benefit from novel animal models, such as CF pigs and ferrets. Prenatal gene therapy is a potential alternative to gene transfer to fully developed lungs. However, unresolved issues, including the possibility of adverse effects on pre- and postnatal development, the risk of initiating oncogenic or degenerative processes and germ line transmission require further investigation. Finally, we discuss the therapeutic potential of stem cells for CF lung disease.

Journal article

Buckley SMK, Rahim AA, Chan JKY, David AL, Peebles DM, Coutelle C, Waddingtont SNet al., 2011, Recent advances in fetal gene therapy., Ther Deliv, Vol: 2, Pages: 461-469, ISSN: 2041-5990

Over the first decade of this new millennium gene therapy has demonstrated clear clinical benefits in several diseases for which conventional medicine offers no treatment. Clinical trials of gene therapy for single gene disorders have recruited predominantly young patients since older subjects may have suffered irrevocablepathological changes or may not be available because the disease is lethal relatively early in life. The concept of fetal gene therapy is an extension of this principle in that diseases in which irreversible changes occur at or beforebirth can be prevented by gene supplementation or repair in the fetus or associated maternal tissues. This article ccnsiders the enthusiasm and skepticism held for fetal gene therapy and its potential for clinical application. It coversa spectrum of candidate diseases for fetal gene therapy including Pompe disease, Gaucher disease, thalassemia, congenital protein C deficiency and cystic fibrosis. It outlines successful and not-so-successful examples of fetal gene therapy in animal models. Finally the application and potential of fetal gene transfer as a fundamental research tool for developmental biology and generation of somatic transgenic animals is surveyed.

Journal article

Argyros O, Wong SP, Fedonidis C, Tolmachov O, Waddington SN, Howe SJ, Niceta M, Coutelle C, Harbottle RPet al., 2011, Development of S/MAR minicircles for enhanced and persistent transgene expression in the mouse liver, Journal of molecular medicine (Berlin, Germany), Vol: 89(5), Pages: 515-529

We have previously described the development of a scaffold/matrix attachment region (S/MAR) episomal vector system for in vivo application and demonstrated its utility to sustain transgene expression in the mouse liver for at least 6 months following a single administration. Subsequently, we observed that transgene expression is sustained for the lifetime of the animal. The level of expression, however, does drop appreciably over time. We hypothesised that by eliminating the bacterial components in our vectors, we could improve their performance since bacterial sequences have been shown to be responsible for the immunotoxicity of the vector and the silencing of its expression when applied in vivo. We describe here the development of a minimally sized S/MAR vector, which is devoid of extraneous bacterial sequences. This minicircle vector comprises an expression cassette and an S/MAR moiety, providing higher and more sustained transgene expression for several months in the absence of selection, both in vitro and in vivo. In contrast to the expression of our original S/MAR plasmid vector, the novel S/MAR minicircle vectors mediate increased transgene expression, which becomes sustained at about twice the levels observed immediately after administration. These promising results demonstrate the utility of minimally sized S/MAR vectors for persistent, atoxic gene expression.

Journal article

Wong SP, Argyros O, Coutelle C, Harbottle RPet al., 2011, Non-viral S/MAR vectors replicate episomally in vivo when provided with a selective advantage, GENE THERAPY, Vol: 18, Pages: 82-87, ISSN: 0969-7128

Journal article

Al-Allaf FA, Coutelle C, Waddington SN, David AL, Harbottle R, Themis Met al., 2010, LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives., Int Arch Med, Vol: 3

Coronary artery diseases (CAD) inflict a heavy economical and social burden on most populations and contribute significantly to their morbidity and mortality rates. Low-density lipoprotein receptor (LDLR) associated familial hypercholesterolemia (FH) is the most frequent Mendelian disorder and is a major risk factor for the development of CAD. To date there is no cure for FH. The primary goal of clinical management is to control hypercholesterolaemia in order to decrease the risk of atherosclerosis and to prevent CAD. Permanent phenotypic correction with single administration of a gene therapeutic vector is a goal still needing to be achieved. The first ex vivo clinical trial of gene therapy in FH was conducted nearly 18 years ago. Patients who had inherited LDLR gene mutations were subjected to an aggressive surgical intervention involving partial hepatectomy to obtain the patient's own hepatocytes for ex vivo gene transfer with a replication deficient LDLR-retroviral vector. After successful re-infusion of transduced cells through a catheter placed in the inferior mesenteric vein at the time of liver resection, only low-level expression of the transferred LDLR gene was observed in the five patients enrolled in the trial. In contrast, full reversal of hypercholesterolaemia was later demonstrated in in vivo preclinical studies using LDLR-adenovirus mediated gene transfer. However, the high efficiency of cell division independent gene transfer by adenovirus vectors is limited by their short-term persistence due to episomal maintenance and the cytotoxicity of these highly immunogenic viruses. Novel long-term persisting vectors derived from adeno-associated viruses and lentiviruses, are now available and investigations are underway to determine their safety and efficiency in preparation for clinical application for a variety of diseases. Several novel non-viral based therapies have also been developed recently to lower LDL-C serum levels in FH patients. This article r

Journal article

Rahim AA, Wong AMS, Buckley SMK, Chan JKY, David AL, Cooper JD, Coutelle C, Peebles DM, Waddington SNet al., 2010, In utero gene transfer to the mouse nervous system., Biochem Soc Trans, Vol: 38, Pages: 1489-1493

The cellular and molecular environment present in the fetus and early newborn provides an excellent opportunity for effective gene transfer. Innate and pre-existing anti-vector immunity may be attenuated or absent and the adaptive immune system predisposed to tolerance towards xenoproteins. Stem cell and progenitor cell populations are abundant, active and accessible. In addition, for treatment of early lethal genetic diseases of the nervous system, the overarching advantage may be that early gene supplementation prevents the onset of irreversible pathological changes. Gene transfer to the fetal mouse nervous system was achieved, albeit inefficiently, as far back as the mid-1980s. Recently, improvements in vector design and production have culminated in near-complete correction of a mouse model of spinal muscular atrophy. In the present article, we review perinatal gene transfer from both a therapeutic and technological perspective.

Journal article

Argyros O, Wong S-P, Fedonidis C, Tolmachov O, Waddington S, Howe S, Coutelle C, Harbottle Ret al., 2010, Development of Scaffold/Matrix Attachment Region(S/MAR) Minicircles for Enhanced and PersistentTransgene Expression in the Mouse Liver, 17th Annual Meeting of German Society for Gene Therapy (DG-GT e.V.), Publisher: Mary Ann Liebert Inc Publishers, Pages: 1197-1198

Conference paper

David AL, Abi-Nader KN, Weisz B, Shaw SWS, Themis M, Cook T, Coutelle C, Rodeck CH, Peebles DMet al., 2010, Ultrasonographic development of the fetal sheep stomach and evaluation of early gestation ultrasound-guided in utero intragastric injection., Taiwan J Obstet Gynecol, Vol: 49, Pages: 23-29

OBJECTIVE: Safely targeting the fetal gastrointestinal tract during early gestation is essential to develop effective prenatal gene therapy for gastrointestinal diseases. In this study, we aimed to characterize the development of the fetal sheep stomach sonographically and to determine the optimum gestational age, as well as the shortterm morbidity and mortality of early-gestation ultrasound-guided intragastric injection. MATERIALS AND METHODS: In experiments investigating ultrasound-guided prenatal gene therapy, we studied the size and development of the stomach of 185 sheep fetuses (33-144 days' gestational age [GA]; term is 145 days). Ultrasound-guided intragastric injection was performed in 12 fetuses at 55-62 days' GA and postmortem examinations were performed 48 hours later. RESULTS: The stomach was not visible at or before 40 days' GA, but it was seen in all fetuses at 55 days' GA or more. The anteroposterior, transverse and longitudinal diameters of the stomach increased in a quasi-linear fashion throughout gestation. Intragastric injection was successful in 10 out of the 11 fetuses (91%) injected at 60-62 days' GA, with nine fetuses (91%) surviving this procedure. CONCLUSION: In the early-gestation sheep fetus, ultrasound-guided intragastric injection has a good success rate with a low short-term mortality and morbidity.

Journal article

Wong SP, Argyros O, Coutelle C, Harbottle RPet al., 2009, Strategies for the episomal modification of cells, CURRENT OPINION IN MOLECULAR THERAPEUTICS, Vol: 11, Pages: 433-441, ISSN: 1464-8431

Journal article

Coutelle C, 2009, From mould to man Edward Lewis Tatum’s vision of the future of medicine, Cellular Therapy and Transplantation (CTT), Vol. 1, No. 4, 2009, Vol: 1

Journal article

Argyros O, Wong SP, Niceta M, Waddington SN, Howe SJ, Coutelle C, Miller AD, Harbottle RPet al., 2008, Persistent episomal transgene expression in liver following delivery of a scaffold/matrix attachment region containing non-viral vector, GENE THERAPY, Vol: 15, Pages: 1593-1605, ISSN: 0969-7128

Journal article

Buckley SMK, Howe SJ, Rahim AA, Buning H, McIntosh J, Wong S-P, Baker AH, Nathwani A, Thrasher AJ, Coutelle C, McKay TR, Waddington SNet al., 2008, Luciferin detection after intranasal vector delivery is improved by intranasal rather than intraperitoneal luciferin administration., Hum Gene Ther, Vol: 19, Pages: 1050-1056

In vivo bioimaging of transgenic luciferase in the lung and nose is an expedient method by which to continually measure expression of this marker gene after gene transduction. Its substrate, luciferin, is typically injected into the peritoneal cavity before bioimaging. Here we demonstrate that, compared with intraperitoneal injection, intranasal instillation of luciferin confers approximately an order of magnitude increase in luciferase bioluminescence detection in both lung and nose. This effect was observed after administration of viral vectors based on adenovirus type 5, adeno-associated virus type 8, and gp64-pseudotyped HIV lentivirus and, to a lesser extent, after nonviral polyethylenimine (PEI)-DNA delivery. Detection increased relative to the concentration of luciferin; however, a standard concentration of 15 mg/ml was well beyond the saturation point. Compared with intraperitoneal injection, intranasal instillation yields about a 10-fold increase in sensitivity with an approximate 30-fold reduction in luciferin usage when bioimaging in the nasal and pulmonary airways of mice.

Journal article

Buckley SM, Howe SJ, Wong SP, Buning H, McIntosh J, Baker A, Nathwani AC, Thrasher A, Coutelle C, McKay TR, Waddington Set al., 2008, Luciferin detection after intra-nasal vector delivery is improved by intra-nasal rather than intra-peritoneal luciferin administration., Hum Gene Ther

In vivo bioimaging of transgenic luciferase in the lung and nose is an expedient method of continually measuring expression of this marker gene after gene transduction. Standardly, its substrate, luciferin, is injected into the peritoneal cavity prior to bioimaging. Here we demonstrate that, compared with intra-peritoneal injection, intra-nasal instillation of luciferin confers approximately an order of magnitude increase in luciferase bioluminescence detection in both lung and nose. This effect was observed following administration of viral vectors based on adenovirus-5, AAV8 and gp64-pseudotyped HIV lentivirus and, to a lesser extent, after non-viral PEI DNA delivery. Detection increased relative to the concentration of luciferin however a standard concentration of 15 mg/ml was well beyond the saturation point. Compared with intra-peritoneal injection, intra-nasal instillation yields around a ten-fold increase in sensitivity with an approximate thirty-fold reduction in the luciferin usage when bioimaging in the nasal and pulmonary airways of mice.

Journal article

Buckley SMK, Howe SJ, Sheard V, Ward NJ, Coutelle C, Thrasher AJ, Waddington SN, McKay TRet al., 2008, Lentiviral transduction of the murine lung provides efficient pseudotype and developmental stage-dependent cell-specific transgene expression., Gene Ther, Vol: 15, Pages: 1167-1175

Gene transfer for cystic fibrosis (CF) airway disease has been hampered by the lung's innate refractivity to pathogen infection. We hypothesized that early intervention with an integrating gene transfer vector capable of transducing the lung via the lumen may be a successful therapeutic approach. An HIV-based lentiviral vector pseudotyped with the baculovirus gp64 envelope was applied to the fetal, neonatal or adult airways. Fetal intra-amniotic administration resulted in transduction of approximately 14% of airway epithelial cells, including both ciliated and non-ciliated epithelia of the upper, mid and lower airways; there was negligible alveolar or nasal transduction. Following neonatal intra-nasal administration we observed significant transduction of the airway epithelium (approximately 11%), although mainly in the distal lung, and substantial alveolar transduction. This expression was still detectable at 1 year after application. In the adult, the majority of transduction was restricted to the alveoli. In contrast, vesicular stomatitis virus glycoprotein pseudotyped virus transduced only alveoli after adult and neonatal application and no transduction was observed after fetal administration. Repeat administration did not increase transduction levels of the conducting airway epithelia. These data demonstrate that application at early developmental stages in conjunction with an appropriately pseudotyped virus provides efficient, high-level transgene expression in the murine lung. This may provide a modality for treatment for lung disease in CF.

Journal article

Buckley SMK, Waddington SN, Jezzard S, Bergau A, Themis M, MacVinish LJ, Cuthbert AW, Colledge WH, Coutelle Cet al., 2008, Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred CFTR-knockout mice., Mol Ther, Vol: 16, Pages: 819-824

Due to its early onset and severe prognosis, cystic fibrosis (CF) has been suggested as a candidate disease for in utero gene therapy. In 1997, a study was published claiming that to how transient prenatal expression of CF transmembrane conductance regulator (CFTR) from an in utero-injected adenovirus vector could achieve permanent reversal of the CF intestinal pathology in adult CF knockout mice, despite the loss of CFTR transgene expression by birth. This would imply that the underlying cause of CF is a prenatal defect for which lifelong cure can be achieved by transient prenatal expression of CFTR. Despite criticism at the time of publication, no independent verification of this contentious finding has been published so far. This is vital for the development of future therapeutic strategies as it may determine whether CF gene therapy should be performed prenatally or postnatally. We therefore reinvestigated this finding with an identical adenoviral vector and a knockout CF mouse line (Cftr(tmlCam)) with a completely inbred genetic background to eliminate any effects due to genetic variation. After delivery of the CFTR-expressing adenovirus to the fetal mouse, both vector DNA and transgenic CFTR expression were detected in treated animals postpartum but statistically no significant difference in survival was observed between the Cftr(-/-) mice treated with the CFTR-adenovirus and those treated with the control vector.

Journal article

Argyros O, Wong SP, Nicetta M, Waddington SN, Coutelle C, Miller AD, Harbottle RPet al., 2008, Persistent episomal transgene expression in liver following hydrodynamic delivery of S/MAR-Containing plasmid DNA, 5th Annual Conference of the British-Society-for-Gene-Therapy, Publisher: MARY ANN LIEBERT INC, Pages: 399-399, ISSN: 1043-0342

Conference paper

Buckley SMK, Waddington SN, Jezzard S, Bergau A, Themis M, MacVinish LJ, Cuthbert AW, Colledge WH, Coutelle Cet al., 2008, Intra-amniotic delivery of CFTR expressing adenovirus does not reverse Cystic Fibrosis phenotype in inbred CFTR-knockout mice, 5th Annual Conference of the British-Society-for-Gene-Therapy, Pages: 414-414

Conference paper

Coutelle C, 2008, Why bother? Is in utero gene therapy worth the effort?, Mol Ther, Vol: 16, Pages: 219-220

Journal article

Coutelle C, 2008, Why Bother?: Is In Utero Gene Therapy Worth the Effort?, Mol Ther, Vol: 16, Pages: 219-220

Journal article

Argyros O, Wong SP, Niceta M, Waddington S, Coutelle C, Miller A, Harbottle Ret al., 2007, Persistent episomal transgene expression in liver following hydrodynamic delivery of S/MAR-containing plasmid DNA, 15th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy, Pages: 990-990

Conference paper

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