Advice Explanation of the COGEM formula for calculating free lentiviral or gammaretroviral vector particles after ex vivo transduction

In biomedical or clinical research, cells are often genetically modified using lentiviral or retroviral vectors, which are genetically modified (GM) viruses. These GM viruses can integrate their genome into a cell’s genome and incorporate a gene of interest. Although genetically modified cells often undergo various cultivation and washing steps after treatment with GM vectors, ‘free’  vector particles (particles not taken up by the cell) may remain present. The presence of these particles poses a potential risk to third parties if they are accidentally exposed to them. Depending on the number of particles present, measures may be necessary to prevent exposure. The number of remaining lentiviral or retroviral vector particles after cultivation and washing can be determined experimentally or theoretically. An experimental approach is preferred but not always possible. In such cases, the ‘COGEM formula’ can be applied.

COGEM has noted that the COGEM formula is not always applied correctly. For some applicants, it also appears to be unclear how the formula’s outcome (the reduction ratio) relates to the number of free vector particles. To clarify the formula’s use, COGEM provides a more detailed explanation in this advisory report and outlines its limitations.