IPEC e-newsletter - Excipients Insight September 2017 - 19-09-17


Inside this issue


Excipients used to stabilise new viral vector for gene therapy

Excipients have been used to stabilise viruses used to transfer genetic sequences into cells – for example for gene therapy – in a development that could make an improved vector suitable for development as biologic therapies.

The research by scientists at Oklahoma State and Kansas Universities in the US is focusing on adenovirus, and specifically a form of the virus known as "fibreless adenovirus" in which proteins found in the organism that contribute to undesirable characteristics such as immune stimulation are stripped out. Removing those proteins also allow modifications to the virus to improve its therapeutic characteristics

Adenoviral vectors have featured prominently in gene therapy experiments – used in upwards of 400 clinical trials – but have been associated with side effects, including the death of a patient enrolled in a gene transfer trial at the University of Pennsylvania in 1999. Fibreless versions of these viruses have been proposed as an alternative, but removing the fibre leads to serious stability issues.

"There is clearly a need to stabilize fibreless adenovirus so that it can serve as a platform for improved adenovirus-based therapies," write the researchers in the Journal of Pharmaceutical Sciences. "Currently, a stable formulation of fibreless adenovirus has not been described."

The team screened various excipients to find candidates that could stabilize the fibreless adenovirus by measuring their ability to improve thermal; stability and prevent aggregation – which leads to a loss of protein activity - and improve the retention of their biological activity. The best excipients were found to be the nonionic surfactant Pluronic F-68 and glycine.

"The work presented here demonstrates that it is possible to enhance the stability of the fibreless adenovirus, which can result in a longer shelf life and, consequently, more consistency in therapeutic efficacy," conclude the researchers.

"We showed that a simple formulation, such as addition of a single excipient, can significantly increase the particle stability and retain the biological activity of the virus."




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