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Results and Publications

TargetAMD results in brief    –  www.cordis.eu

AMD is a chronic progressive condition that results from age-related alterations in the retina. There are two types of AMD: a slow-progressing, non-vascular form and a rapidly progressing, blinding form. In the latter, high levels of VEGF and low levels of PEDF, an inhibitor of vascularisation and potent neurotrophic factor, have been observed.

Based on this, current treatment consists of monthly injections of anti-VEGF antibodies or inhibitors. However, the high cost and low efficacy of this approach demands a viable therapeutic alternative.

Research teams on the EU-funded ‘Transposon-based, targeted ex vivo gene therapy to treat age-related macular degeneration (AMD)’ project propose to transplant GMP-grade genetically modified cells that overexpress PEDF in a First-In-Man clinical trial as a life-long therapeutic solution for AMD. The personalised procedure entails introduction of the human PEDF gene into autologous iris pigment epithelial cells ex vivo, and transplantation into the sub-retinal space of AMD patients. For this purpose, they are using the non-viral Sleeping Beauty transposon system that has the capacity to integrate into the host cell’s genome.

Preclinical studies could be successfully accomplished proving consistency of a Gene Therapy Medicinal Product (GTMP) of highest quality and confirming safety and efficacy of the approach in vivo in 3 different species and models. Development and production of novel devices, reagents and plasmids have been successfully completed. In a recent Presubmission Meeting where the preclinical data was presented and discussed, the Swiss regulatory authority confirmed appropriateness of preclinical data toward the clinical trial.

Therefore, the TARGETAMD partners are confident that the major challenge of the procedure, which is associated with the small number of isolated cells, has been successfully surmounted and are optimistic that the phase Ib/IIa clinical trial for the treatment of AMD using genetically modified autologous cells will revolutionise therapeutic outcome.

Peer-reviewed publications

 Thumann et al. Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the SB Transposon System Delivered by pFAR4 Plasmids. Mol Ther Nucleic Acids. 2017. 6:302-314.

Hudecek et al. Going non-viral: the Sleeping Beauty transposon system breaks on through to the clinical side. Crit Rev Biochem Mol Biol. 2017. 12:1-26.

Stolba et al. Neovascular AMD in Austria – an expert review – and introduction to the TargetAMD approach. Spektrum der Augenheilkunde. Resubmitted after “accepted with minor comments”.

Fernandez-Robredo et al. Long-term PEDF release in rat iris and retinal epithelial cells after Sleeping Beauty transposon-mediated gene delivery. Mol Ther Nucleic Acids. Under revision

Pastor et al. The antibiotic-free pFAR4 vector merged with the Sleeping Beauty transposon system mediates efficient transgene delivery in human cells. In preparation.

Citable abstracts

Citable abstracts 2012-2017

Dissemination activities

Partner Act. Title Date Place Audience
UNIGE PRE Séance publique d’information aux patients 2012-12-06 2013-03-14 2013-05-23 2013-11-21 2014-01-16 Geneva (CH) Patients
UNIGE PRE Journée de la rétine (La thérapie génique: espoir ou illusion?) 2012-03-21 Coppet (CH) Clinicians
UNIGE COLL
PRE
Neuroclinique colloquium (Non-viral Gene-therapeutic Approach to Treat AMD – The TargetAMD Project) 2012-04-17 Geneva (CH) Neuro- logists
CNRS CONF
PRE
ESGCT-SFTCG Conference 2012-10-25 Paris (FR) Scientific Community
UNIGE COLL
PRE
Internists colloquium (Dégénérence Maculaire Liée à l’Âge (DMLA)) 2012-09-24 Geneva (CH) Internists
UKA PRE Electrochemotherapy, 2nd International Users’ Meeting 2013-03-01 -2013-03-02 Bologna (I) Scientific Community
UNIGE LECT
PRE
Pathologies vitréorétinienne 2013 Geneva (CH) Students
UNIGE TRAI
PRE
Colloquium for nurses 2013-04-18 Geneva (CH) Nurses
UNIGE CONF
PRE
DOC (Cell-based Therapy for the Treatment of Retinal Degeneration) 2013-05-15 -2013-05-17 Nurem- berg (GER) Scientific community
CNRS CONF
PRE
ASGCT – American Society of Cell and Gene Therapy 2013-05-18 Salt Lake City (US) Scientific Community
UNIGE PRE Leçon inaugurale (La thérapie génique: espoir ou illusion?) 2013-05-23 Geneva (CH) Employees of the UNIGE
UNIGE ARTI Pulsations (Espoir pour la DMLA) 2013-05-01 Geneva (CH) Public
UNIGE CONF
PRE
SOE (Cell-based Therapy for the Treatment of Retinal Degeneration) 2013-06-08 -2013-06-11 Copen- hagen (DK) Scientific community
KAR PRE SOE, Retina showcase (Human retinal pigment epithelial transplantation – are we too slow? 2013-06-08 -2013-06-11 Copen- hagen (DK) Scientific community
KAR PRE Deutsche Ophthalmochirurgen; Symposium on cell therapies: Human RPE Transplantation- are we too slow? 2013-06-12 -2013-06-14 Nuremberg (GER) Scientific community
UKA PRE 25. Aachener Dialog, “Hinterabschnittserkrankungen” 2013-06-19 Aachen (GER) Ophthal- mologists
KAR PRE Deutsche Ophthalmologische Gesellschaft 2013-09-16 Berlin (GER) Ophthal- mologists
UKA CONF
PRE
POS
Conference on Transposition and Genome Engineering 2013-09-18 Budapest (HUN) Scientific Community
MDC PEI CONF
POS
Conference on Transposition and Genome Engineering: (Transposon-Mediated PEDF Gene Delivery into Primary Pigment Epithelial Cells for the Treatment of Retinal Degenerative Diseases) 2013-09-18 -2013-09-21 Budapest (HUN) Scientific community
UNIGE PRE Age-related Macular Degeneration 2013-10-17 Geneva (CH) Employees of the UNO
UKA PRE
POS
European Society of Gene & Cell Therapy 2013-10-25 -2013-10-28 Madrid (ESP) Scientific Community
UNIGE CONF
POS
ESGCT and SETGyC collaborative congress 2013-10-25 -2013-10-28 Madrid (ES) Scientific Community
UKA CONF
POS
ESGCT and SETGyC collaborative congress 2013-10-25 -2013-10-28 Madrid (ES) Scientific Community
CNRS POS Conference on Transposition and Genome Engineering – 2013 2013-09-18 -2013-09-21 Budapest (HUN) Scientific Community
CNRS POS European Society of Gene & Cell Therapy Conference -2013 2013-10-25 -2013-10-28 Madrid (ES) Scientific Community
CNRS CONF
PRE
BIT’s 4th Worlg Gene Convention) 2013-11-13 Haikou (CHN) Scientific Community
CNRS CONF
LECT
Lecture to students – Master of Gene and Cell Therapy 2013-11-07 Paris XII University (FR) Students
CNRS CONF Lecture to students on Biomedicines 2013-11-26 Paris (FR) Students
CNRS WS Workshop on Gene Therapy 2013-11-26 Doha (QA) Scientific Community
CNRS SEM Hadassah Medical School 2013-12-02 Jerusalem (ISR) Scientific Community
CNRS SEM Weizmann Institute 2013-12-04 Rehovot (ISR) Scientific Community
CNRS CONF Lecture to students – Master of Biotherapies 2014-01-13 Paris XI University (FR) Scientific Community
CNRS LECT Lecture to Master students in Biomedicine 2014-01-28 – ESPCI- ParisTech (FR) Students
CNRS CONF E-rare Symposium 2014-01-21 Athens (GRC) Scientific Community
CNRS CONF History of plasmid size reduction Plenary Introductory lecture – Minicircle & DNA Vector Conference – 2014 2014-01-28 Bielefeld (GER) Scientific Community
UNIGE POS Société Française de Thérapie Cellulaire et Génique 2014-03-19 Toulouse (Fr) Scientific Community
UNIGE CONF Retina 2014 2014-03-29 Rome (I) Scientific Community
CNRS CONF Minicircle & DNA Vector Conference – 2014 2014-05-07 -2014-05-09 Bielefeld (GER) Scientific Community
UKA POS
PRE
Association for Research in Vision and Ophthalmology 2014-05-04 -2014-05-08 Orlando, Florida (US) Scientific Community
UNIGE CONF Jules Gonin 2014 2014-05-09 Zurich (CH) Scientific Community
CNRS POS American Society of Gene & Cell Therapy Conference – 2014 2014-05-21 -2014-05-24 Washing- ton (US) Scientific Community
GenoS WEB Presentation of the Project in the GenoSafe new website June 2014 Web Public
UNIGE SEM Lecture to ophthalmologists 2014-09-09 Geneva (CH) Ophthal- mologists
CNRS LECT Université Paris-Descartes Biotherapy 2014-09-28 Paris (FR) Students
UN CONF EVER 2014. European association for vision and eye research 2014-10-01 -2014-10-04 Nice (I) Scientific community
UNIGE POS ESGCT – NVGC Joint meeting The Hague 2014-10-22 -2014-10-26 The Hague (NL) Scientific Community
GenoS NEWL Presentation of the Project in the GenoSafe Newsletter 2014-10-20 Scientific Community
UN CONF Use of Antibiotic-Resistance-Free Plasmids for Non-Viral Transfection of Pigment Epithelium-Derived Factor in Rat Primary Cells. 2014 Nice
(FR)
Scientific Community
UNIGE PRE Diabetic Retinopathy 2014-11-13 Geneva (CH) Employees of the UNO
UNIGE PRE IFA – Innsbrucker Fortbildung für Augenärzte: Gene-Therapy instead of Avastin 2014-11-15 Insbruck (AUS) Scientific Community
UNIGE PRE Ex vivo Gene Therapy for the Treatment of exudative Age-Related Macular Degeneration (Retina Now – Novartis Symposium) 2015-03-05 Berne (CH) Scientific Community
UNIGE PUB Gentherapie statt Anti-VEGF bei AMD (Ophthalmologische Nachrichten, Apr 2015) 2015-04-01 Germany Scientific Community
UKA POS Analysis of Potential Tumorigenicity of PEDF-Transfected Primary Human Retinal Pigment Epithelial Cells Using Soft Agar Assay (Association for Research in Vision and Ophthalmology – ARVO 2015) 2015-05-04 Denver (USA) Scientific Community
UN POS Biodistribution of Rat Primary Cells transfected with SB100X transposon-mediated Pigment Epithelium-Derived Factor (PEDF) gene in Brown Norway rats after subretinal injection (ARVO 2015) 2015-05-03 Denver (USA) Scientific Community
UNIGE POS The use of mini-plasmids free of antibiotic resistance markers for a gene therapeutical approach to treat AMD (ARVO 2015) 2015-05-03 Denver (USA) Scientific Community
UNIGE POS pFAR4 miniplasmids in combination with the Sleeping Beauty transposon system allow efficient transfection of freshly isolated iris pigment epithelial cells (ARVO 2015) 2015-05-03 Denver (USA) Scientific Community
UNIGE POS Transposon-Based, Targeted Ex Vivo Gene Therapy to Treat Age-Related Macular Degeneration (ARVO 2015) 2015-05-03 Denver (USA) Scientific Community
UNIGE PRE Gene therapy in ophthalmology – the TargetAMD project (TEDD Symposium – Frontiers in Personalized Medicine) 2015-06-18 Wädenswil (CH) Scientific Community
UNIGE PUB Gene therapy for the eye: the TargetAMD project (CHIMIA 2015, 69, No. 7/8, 491-493) 2015-08-17 Berne (CH) Scientific Community
CNRS PRES 1st World Congress on Electroporation 2015-09-06 Portoroz, Slovenia Scientific Community
UKA POS pFAR4/SB100X-mediated PEDF gene delivery in primary murine pigment epithelial cells (European Society of Gene & Cell Therapy – ESGCT 2015) 2015-09-17 Helsinki (FN) Scientific Community
UNIGE POS Over-expression of PEDF by PEDF-transfected primary pigment epithelial cells does not induce tumorigenicity (ESGCT 2015) 2015-09-17 Helsinki (FN) Scientific Community
UNIGE POS Stable genomic integration of PEDF in primary pigment epithelial cells transfected with the Sleeping Beauty transposon system to treat age-related macular degeneration (AMD)(ESGCT 2015) 2015-09-17 Helsinki (FN) Scientific Community
UNIGE PRE The TargetAMD project – Using Free of antibiotic resistance gene (pFAR4) miniplasmids for a Sleeping Beauty (SB100X) mediated gene therapy to treat neovascular Age-Related Macular Degeneration (nAMD) (ESGCT 2015) 2015-09-17 Helsinki (FN) Scientific Community
UNIGE
RWTH
UKA
POS Information poster TargetAMD (firstly presented: ESGCT 2015) 2015-09-17 Helsinki (FN) Scientific Community
UNIGE
RWTH
UKA
FLY Information flyer TargetAMD (firstly presented: ESGCT 2015) 2015-09-17 Helsinki (FN) Scientific Community
UKA POS Lack of Tumorigenic Potential of PEDF Transfected Primary Human Pigment Epithelial Cells in Soft Agar Assays 2015-10-04-01 Berlin (GER) Scientific Community
UNIGE ART Gentherapie zur Behandlung der nAMD: das TargetAMD Projekt 2016-01 (GER) Scientific Community
UNIGE LECT Transposon-based ex vivo gene therapy to treat age-related macular degeneration 2016-01-21 Neuchâtel (CH) Scientific Community
UKA LECT Nicht-virale ex vivo Gentherapie zur Behandlung der neovaskulären altersbedingten Makuladegeneration (178. Versammlung des Vereins Rheinisch-Westfälischer Augenärzte – RWA 2016) 2016-01-30 Bonn(GER) Scientific Community
UNIGE LECT Status quo of TargetAMD_RPE at KAR (GM TargetAMD Consortium) 2016-04-22 (CH) Scientific Community
KAR LECT Presentation of TargetAMD_RPE to ophthalmologists and optometrists (Eye Dept., KAR) 2016-04-28 (AUS) Scientific Community
UN POS Efficacy of Rat Primary Cells transfected with Pigment Epithelium-Derived Factor using the Sleeping BeautyTransposon system in choroidal neovascularization (ARVO 2016) 2016-04-30 Seattle (USA) Scientific Community
UNIGE POS Results of a biodistribution study of Venus transfected pigment epithelial cells transplanted subretinally in rabbits (ARVO 2016) 2016-04-30 Seattle (USA) Scientific Community
UNIGE POS Human PEDF optimized gene for transposon-based gene therapy to treat age-related macular degeneration (ARVO 2016) 2016-04-30 Seattle (USA) Scientific Community
UNIGE POS Optimized Non-Viral Transfection of human RPE and IPE cells used for a Gene-Therapeutic Treatment of neovascular AMD (ARVO 2016) 2016-04-30 Seattle (USA) Scientific Community
KAR LECT Presentation of TargetAMD_RPE to Pharmacists 2016-05-03 (AUS) Scientific Community
PEI LECT The Sleeping Beauty Transposon System for Molecular Therapy (Annual Congress of the American Society of Gene and Cell Therapy, ASGCT) 2016-05-04 Washington (USA) Scientific Community
UNIGE LECT La dégénérescence maculaire liée à l’âge (DMLA) – ses causes et les possibilités de traitement (patient information event) 2016-05-12 Geneva (CH) Scientific Community
UKA LECT Pigment Epithelial Cell-Based Non-Viral Gene Therapeutic Treatment of Neovascular AMD (Cellular and Molecular Neurobiology Study Group Meeting, Uniklinik RWTH Aachen) 2016-05-30 Aachen(GER) Scientific Community
KAR LECT Presentation of TargetAMD_RPE to Laboratory Employees 2016-06-02 (AUS) Scientific Community
UKA LECT TargetAMD Transposon-based, targeted ex vivo gene therapy to treat age-related macular degeneration (Seminar der Klinik für Augenheilkunde, Uniklinik RWTH Aachen) 2016-06-22 Aachen (GER) Scientific Community
UKA LECT Improved pigment epithelial cell-based non-viral gene therapeutic approach for neovascular AMD (Deutsche Ophthalmologische Gesellschaft – DOG Kongress 2016) 2016-06-29 Berlin(GER) Scientific Community
UKA POS Lack of indication for tumorigenicity after pFAR4/SB100X-mediated PEDF gene delivery in primary murine pigment epithelial cells ex vivo (European Society of Gene & Cell Therapy – ESGCT 2016) 2016-10-09 & 10 Florence (I) Scientific Community
UKA POS pFAR4/SB100X-mediated PEDF gene delivery in iris pigment epithelial cells isolated from patients’ iridectomies mimicking a therapeutic approach for the treatment of neovascular AMD (European Society of Gene & Cell Therapy – ESGCT 2016) 2016-10-09 & 10 Florence (I) Scientific Community
UKA POS pFAR4/SB100X-mediated PEDF gene delivery in primary human pigment epithelial cells for the treatment of neovascular AMD (European Society of Gene & Cell Therapy – ESGCT 2016) 2016-10-09 & 10 Florence (I) Scientific Community
UNIGE POS Safety Studies for Cell-Based Gene Therapy (TargetAMD project): In Vivo Exclusion of Tumorigenicity and Proof of Cell Product Quality (European Society of Gene & Cell Therapy – ESGCT 2016) 2016-10-09 & 10 Florence (I) Scientific Community
UNIGE POS Transposon-Based, Targeted Ex Vivo Gene Therapy to Treat Age-related Macular Degeneration: The TargetAMD projectEuropean Society of Gene & Cell Therapy – ESGCT 2016) 2016-10-09 & 10 Florence (I) Scientific Community (European Society of Gene & Cell Therapy – ESGCT 2016)
UNIGE POS Translation of GLP-grade Electroporation of Primary Pigment Epithelial Cells to GMP-grade GTMP Manufacturing for Clinical Use (European Society of Gene & Cell Therapy – ESGCT 2016) 2016-10-09 & 10 Florence (I) Scientific Community
Activities (Act.)
ARTI Artikel in press
COLL Colloquium
CONF Conference
LECT Lecture
NEWL Newsletter
POS Poster
PRE Presentation
SEM Seminar
TRAI Training
WEB Website
WS Workshop