title: The case for intrauterine gene therapy.
abstract: Single-gene disorders can cause perinatal mortality or severe permanent morbidity. Intrauterine gene therapy seeks to correct the genetic defect in the early stages of pathogenesis through delivery of a vector system expressing the therapeutic transgene to the fetus. Advantages of intrauterine gene therapy include prevention of irreversible organ damage, potentially inducing central tolerance and wider bio-distribution, including the brain after delivery of vector. Already, proof-of-cure has been demonstrated in knockout animal models for several diseases. Long-term outcomes pertaining to efficacy and durability of transgene expression and safety are under investigation in clinically relevant non-human primate models. Bystander effects in the mother from transplacental vector trafficking require further assessment. In this chapter, we discuss the candidate diseases amenable to intrauterine gene therapy, current state-of-the-art evidence, and potential clinical applications.
authors: Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Citra N
authors: CN
authors: Mattar
authors: Simon N
authors: SN
authors: Waddington
authors: Arijit
authors: A
authors: Biswas
authors: Andrew M
authors: AM
authors: Davidoff
authors: Mahesh
authors: M
authors: Choolani
authors: Jerry K Y
authors: JK
authors: Chan
authors: Amit C
authors: AC
authors: Nathwani
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000235:genetics*; D005333:Fetus; D018014:Gene Transfer Techniques; D030342:Genetic Diseases, Inborn / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D011247:Pregnancy