Importance of Nonhuman Primates as a Model System for Gene Therapy Development in Ophthalmology

Abstract

Gene therapy is a treatment concept that uses, in most cases, viral vectors to deliver a therapeutic transgene to target cells. Although the idea of gene therapy dates back over 50 years ago, due to the complexity of the treatment concept, it took until the last decade for the responsible agencies like FDA and EMA to recommend the first gene therapy products for clinical use. The development of these therapies relies on molecular engineering of specifically designed vectors and models to test the effectiveness and safety of the treatment. Despite an increasing effort to find effective surrogates, animal models are still irreplaceable in gene therapy development. Rodents are important for exploring pathways and disease mechanisms and identifying potential treatment targets. However, only the primate eye resembles the human eye to a degree where most structures are nearly identical. Some research questions can therefore only be answered using a nonhuman primate (NHP) model. In this review, we want to summarize these key features and highlight the importance of the NHP model for gene therapy development in ophthalmology.

Zusammenfassung

Bei der Gentherapie wird mittels eines meist viralen Vektors ein spezifisch entwickeltes therapeutisches Transgen in bestimmte Zielzellen eingeschleust. Zur Erreichung dieses Ziels waren viele Jahrzehnte an Forschung notwendig und erst seit ungefähr 10 Jahren gibt es die ersten am Menschen zugelassenen Gentherapien. Unverzichtbar für die Entwicklung sind die Methoden der modernen Molekulargenetik und -technik sowie geeignete Tiermodelle. Die zunehmend besseren Alternativen können die gängigen Tiermodelle zum jetzigen Zeitpunkt allerdings noch nicht vollständig ersetzen. Mausmodelle nehmen weiterhin aufgrund ihrer vielen Vorteile eine tragende Rolle ein. Jedoch bestehen grundlegende Unterschiede zur Physiologie und Anatomie insbesondere der Netzhaut des Menschen, weshalb sie für diesbezügliche Fragestellungen nur bedingt geeignet sind. Die Augen der Primaten sind hingegen denen des Menschen in strukturellem Aufbau der Netzhaut und des Auges sehr ähnlich. Dadurch besteht eine deutlich bessere Vergleichbarkeit für bestimmte Fragestellungen in der Entwicklung von Gentherapien am Auge. In diesem Artikel möchten wir die Relevanz von Tiermodellen an sog. nicht menschlichen Primaten in der Entwicklung von Gentherapien am Auge darstellen.

Key words

gene therapy - drug development - animal models

Schlüsselwörter

Gentherapie - Therapieentwicklung - Tiermodell

Publication History

Received: 06 October 2021

Accepted: 16 February 2022

Accepted Manuscript online:
21 February 2022

Article published online:
22 March 2022

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