Retention Rates of Genetic Therapies Based on AAV Serotypes 2 and 8 Using Different Drug-Delivery Materials

TL;DR

This study compares how well different tools retain gene therapy agents during eye injections, finding similar performance across various devices.

Contribution

The study provides a direct comparison of retention rates for AAV2 and AAV8 gene therapies using different subretinal injection systems.

Findings

Retention rates for VN and AAV8 vectors were comparable across tested cannulas.

PolyTip® and DORC devices showed similar retention rates for both AAV serotypes.

Test–retest variability for DORC products was low, indicating consistent performance.

Abstract

The purpose of this study was to compare the retention rate of Adeno-associated viral vector (AAV) gene therapy agents within different subretinal injection systems. The retention of AAV serotype 2-based voretigene neparvovec (VN) and a clinical-grade AAV serotype 8 vector within four different subretinal cannulas from two different manufacturers was quantified. A standardized qPCR using the universal inverted terminal repeats as a target sequence was developed. The instruments compared were the PolyTip® cannula 25 g/38 g by MedOne Surgical, Inc., Sarasota, FL, USA, and three different subretinal injection needles by DORC, Zuidland, The Netherlands (1270.EXT Extendible 41G subretinal injection needle (23G), DORC 1270.06 23G Dual bore injection cannula, DORC 27G Subretinal injection cannula). The retention rate of VN and within the DORC products (10–28%) was comparable to the retention rate (32%) found for the PolyTip® cannula that is mentioned in the FDA-approved prescribing information for VN. For the AAV8 vector, the PolyTip® cannula showed a retention rate of 14%, and a similar retention rate of 3–16% was found for the DORC products (test–retest variability: mean 4.5%, range 2.5–20.2%). As all the instruments tested showed comparable retention rates, they seem to be equally compatible with AAV2- and AAV8-based gene therapy agents.

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