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

Felix F Reichel; Peter Kiraly; Immanuel P Seitz; M Dominik Fischer

doi:10.3390/ijms25073705

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

Int J Mol Sci. 2024 Mar 26;25(7):3705. doi: 10.3390/ijms25073705.

Authors

Felix F Reichel^{1

2

3}, Peter Kiraly^{1

2}, Immanuel P Seitz³, M Dominik Fischer^{1

2

3}

Affiliations

¹ Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford OX1 2JD, UK.
² Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK.
³ Centre for Ophthalmology, University Eye Hospital Tübingen, 72076 Tübingen, Germany.

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.

Keywords: AAV; drug delivery; gene therapy; retention; subretinal injection.

MeSH terms

Animals
Dependovirus / genetics
Drug Delivery Systems
Genetic Therapy
Grasshoppers*
Parvovirinae*
Serogroup

Supplementary concepts

Adeno-associated virus-2

Grants and funding

This work was supported by the National Institute for Health and Care Research (NIHR) grant: BRC4 Gene and Cell Therapy. DORC provided the injection instruments free of charge.