The Use of Gene Therapy Tools in Reproductive Immunology Research

Abstract

Mammalian pregnancy is a complex phenomenon allowing the maternal immune system to support its allogeneic fetus, while still being effective against pathogens. Gene therapy approaches have the potential to treat devastating inherited diseases for which there is a little hope of finding a conventional cure. In reproductive medicine, experimental trials have been made so far only for correcting gene defects in utero. The use of gene therapy for improving pregnancy-rate success or avoiding pregnancy-related diseases i.e. miscarriage or pre-eclampsia, remains a very distant goal with unresolved moral and ethical aspects. However, gene therapy may help determining the role of several genes in supporting fetal growth and/or avoiding its rejection experimentally and might further help to identify new targets of intervention. Gene therapy strategies to avoid fetal rejection may include the transfer and expression of cyto-protective molecules locally at the fetal-placental interface. In addition, the ex-vivo genetic modification of immune cells for tolerance induction is a novel and tempting approach. In this regard, we have confirmed the role of the cyto-protective and immunomodulatory molecule Heme Oxygenase-1 (HO-1), by treating animals undergoing abortion with an adenovirus coding for HO-1. Since the sole application of a control vector did not provoke deleterious effects in pregnancy outcome, we propose the use of experimental gene therapy for unveiling molecular and cellular pathways leading to pregnancy success.

Proteomics: A Novel Methodology to Complement Prenatal Diagnosis of Chromosomal Abnormalities and Inherited Human Diseases

“…47 Tremendous advances in the field of genomics by the sequencing of some 25,000 to 40,000 genes paved the way for a better understanding of the underlying cellular and molecular mechanisms responsible for human diseases, and further development of a new medical field, gene therapy. 48,49 Although genomics represents a significant advance, it cannot reflect the enormity and complexity of the human proteome. The concept of one gene-one protein is no longer valid, given that 51% of genes encode more than one protein isoform.…”

Safety of Liver Surface Instillation of Plasmid DNA in Normal and Carbon Tetrachloride-Induced Hepatitis Mice

“…Gene therapy is a promising approach for the treatment of acquired, refractory and fatal diseases as well as inherited gene deficiency diseases (1)(2)(3)(4)(5). Although enthusiastic investigations have been performed, clinical application of gene therapy is still limited.…”