Gene Therapy Medicinal Products (GTMP) cover a broad array of different technologies and product types. The purpose of such therapies is to deliver a genetically engineered construct which will express either a therapeutic sequence or protein to enable the repair, regulation, addition or deletion of a gene sequence. The overall aim being to regulate or modify somatic cells at the genetic level. The earliest gene therapies were DNA plasmid; delivered either in a simple salt formulation (termed ‘naked’ DNA), delivered with a carrier or via a delivery system.

Other types include the use of viral or bacterial vectors to deliver the selected gene sequence (nucleic acid) into the target cells. These therapies have relied on expression of the transgene in the cells.

The more recent gene therapies include microRNA (miRNA), small interfering RNA (siRNA) and short hair pin RNA (shRNA). These therapies exert their effect by interfering with RNA.

Regardless of the type of gene therapy there are some common quality issues which need to be addressed including:

  • Selectivity of the GTMP for the target cells
  • Transduction efficacy
  • Functional activity of the transgene

Given that the genetic sequence needs to be appropriately delivered into the target cell in order to be at the site of action, barriers to the success of the gene therapy factors include: the uptake of the vector, its persistence at the site and sustaining the expression of the transgene. If there is immune response to the vector this can adversely affect its ability to remain in at the target cell and continue to express the transgene.

Overall a fascinating area of therapeutic development – which has some unique regulatory challenges.

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