Benefits and Shortcomings of Laboratory Model Systems in the Development of Genetic Therapies

Kirsten Bucher; Eduardo Rodriguez-Bocanegra; M. Dominik Fischer

doi:10.1055/a-1757-9879

Klinische Monatsblätter für Augenheilkunde, Table of Contents

Klin Monbl Augenheilkd 2022; 239(03): 263-269
DOI: 10.1055/a-1757-9879

Übersicht

Benefits and Shortcomings of Laboratory Model Systems in the Development of Genetic Therapies

Vorteile und Defizite von Labormodellsystemen bei der Entwicklung von Gentherapieverfahren

Kirsten Bucher^*

¹University Eye Hospital, University Hospital Tübingen Clinic of Ophthalmology, Tubingen, Germany

²Institute for Ophthalmic Research, University Hospital Tübingen Clinic of Ophthalmology, Tubingen, Germany

,

Eduardo Rodriguez-Bocanegra^*

¹University Eye Hospital, University Hospital Tübingen Clinic of Ophthalmology, Tubingen, Germany

,

M. Dominik Fischer

¹University Eye Hospital, University Hospital Tübingen Clinic of Ophthalmology, Tubingen, Germany

²Institute for Ophthalmic Research, University Hospital Tübingen Clinic of Ophthalmology, Tubingen, Germany

³Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom of Great Britain and Northern Ireland

⁴Department of Clinical Neurosciences, University of Oxford Nuffield Laboratory of Ophthalmology, Oxford, United Kingdom of Great Britain and Northern Ireland

› Author Affiliations

Abstract

Gene therapeutic approaches promise treatment or even a cure of diseases that were previously untreatable. Retinal gene therapies tested in clinical trials comprise a wide range of different strategies, including gene supplementation therapies, in vivo gene editing, modulation of splicing mechanisms, or the suppression of gene expression. To guarantee efficient transfer of genetic material into the respective target cells while avoiding major adverse effects, the development of genetic therapies requires appropriate in vitro model systems that allow tests of efficacy and safety of the gene therapeutic approach. In this review, we introduce various in vitro models of different levels of complexity used in the development of genetic therapies and discuss their respective benefits and shortcomings using the example of adeno-associated virus-based retinal gene therapy.

Zusammenfassung

Gentherapeutische Ansätze versprechen die Behandlung oder sogar Heilung von Erkrankungen, die bisher nicht behandelbar waren. Die in klinischen Studien getesteten Gentherapien für die Netzhaut umfassen ein breites Spektrum unterschiedlicher Strategien, darunter Genergänzungstherapien, In-vivo-Gene-Editing, Modulation von Splicing-Mechanismen oder die Unterdrückung der Genexpression. Um einen effizienten Transfer des genetischen Materials in die jeweiligen Zielzellen zu gewährleisten und gleichzeitig schwerwiegende unerwünschte Wirkungen zu vermeiden, erfordert die Entwicklung von Gentherapien geeignete In-vitro-Modellsysteme, mit denen die Wirksamkeit und Sicherheit des gentherapeutischen Ansatzes getestet werden kann. In diesem Übersichtsartikel werden verschiedene In-vitro-Modelle unterschiedlicher Komplexität vorgestellt, die bei der Entwicklung von Gentherapien verwendet werden, und ihre jeweiligen Vor- und Nachteile werden am Beispiel der AAV-basierten Gentherapie der Netzhaut diskutiert.

Key words

gene therapy - retina - in vitro model - AAV

Schlüsselwörter

Gentherapie - Netzhaut - In-vitro-Modell - AAV

Full Text

References

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