Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2023

Nucleic acid reference materials for accurate measurements in gene therapy, pandemic preparedness and vaccine development (#115)

Anna Baoutina 1 , Kimberley Dilworth 2 , Jacob McLaughlin 1 , Michael Forbes-Smith 1 , David Lynch 1 , Felicity Hall 1 , Kate Griffiths 1 , Leo Pinheiro 1 , Somanath Bhat 1 , Lina Partis 1 , Leszek Lisowski 2 , Daniel Burke 1
  1. National Measurement Institute, Lindfield, NSW, Australia
  2. Translational Vectorology Research Unit, Children's Medical Research Institute, Westmead, NSW, Australia

Quantitative genetic reference materials (RMs), often referred to as standards, facilitate accurate testing for diseases caused by infections or faulty genes, and for prognosis of their treatment. They are also important in standardised production of genetic vaccines and quantification of gene therapy vectors. There is, however, lack of universal certified RMs for these applications. A particular challenge is to produce genetic RMs with concentration values that are globally consistent and stable over time, as required for traceability to the International System of Units (SI). Traceability to the SI would allow valid comparison of accuracy of testing kits or of concentration of genetic vaccines and gene therapy vectors from different batches or manufacturers, or of data from different research studies.

NMI can produce fit-for-purpose genetic certified RM with globally comparable concentration values. We design and validate accurate and reliable polymerase chain reaction (PCR) assays and corresponding RMs, including synthetic DNA or RNA templates. Our RMs are SI-traceable and their reference value has assigned uncertainty that includes factors for homogeneity, stability and, for RNA RMs, reverse transcription (RT) efficiency. The use of such RMs as calibrants in (RT)-PCR converts Ct values to accurate copy number concentration values.

This presentation describes our recent work on production and evaluation of inactivated SARS-CoV2 virus RM and two synthetic DNA standards for adeno-associated virus-based gene therapy vectors (rAAV). rAAV are becoming important vehicles for clinical gene therapy and their accurate quantification is critical when producing rAAV for clinical use under cGMP standards. We continue working on universal standards for various rAAV serotypes and for lentivirus-based vectors, and on standards for several organisms of concern for future pandemics.

NMI collaborates with public health and pathology laboratories, kit manufacturers and proficiency test providers. We look for partners within Australia and globally that can benefit from our unique capabilities.