1052. Male Germline Cells Appear To Be at Risk Following Direct Injection Gene Transfer In Utero

The successful transduction of hematopoietic stem cells and long-term (28 months) transgene expression within the hematopoietic system following the direct injection of high-titer retroviral vectors into preimmune fetal sheep was previously demonstrated. The present studies extended these analyses for 40 months postinjection and evaluated whether the longevity of transgene expression in this model system was the result of induction of prenatal tolerance to the transgene product. The intraperitoneal injection of retroviral vectors into preimmune sheep fetuses transduces thymic epithelial cells thought to present antigen and thus define self during immune system development. To directly demonstrate induction of tolerance, postnatal sheep were boosted with purified β-galactosidase and showed that the peripheral blood lymphocytes from in utero–transduced sheep exhibited significantly lower stimulation indices to transduced autologous cells than did control animals and that the in utero–transduced sheep had a reduced ability to mount an antibody response to the vector-encoded β-galactosidase protein compared with control sheep. Collectively, our results provide evidence that the direct injection of retroviral vectors into preimmune sheep fetuses induces cellular and humoral tolerance to the vector/transgene products and provide an explanation for the duration and stability of transgene expression seen in this model. These results also suggest that even relatively low levels of gene transfer in utero may render the recipient tolerant to the exogenous gene and thus potentially permit the successful postnatal treatment of the recipient.

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Faculty Opinions recommendation of Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2426977.2703084 ◽

2010 ◽

Author(s):

Alain Prochiantz

Keyword(s):

Gene Transfer ◽

Frontal Cortex ◽

In Utero ◽

Behavioral Deficits

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Feasibility of Retroviral Vector-Mediated in utero Gene Transfer to the Fetal Rabbit

Fetal Diagnosis and Therapy ◽

10.1159/000088036 ◽

2005 ◽

Vol 20 (6) ◽

pp. 485-493 ◽

Cited By ~ 5

Author(s):

Rafael Moreno ◽

Marta Rosal ◽

Lluis Cabero ◽

Eduard Gratacós ◽

Josep M. Aran

Keyword(s):

Gene Transfer ◽

Retroviral Vector ◽

In Utero

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Tetracycline syrups and children’s teeth

Drug and Therapeutics Bulletin ◽

10.1136/dtb.22.14.55 ◽

1984 ◽

Vol 22 (14) ◽

pp. 55-56

Keyword(s):

At Risk ◽

In Utero ◽

Permanent Teeth ◽

Deciduous Teeth ◽

Enamel Hypoplasia ◽

Yellow Colour ◽

Paediatric Patients ◽

Short Course

It has been known for over 25 years that treatment with oral tetracyclines can permanently stain children’s teeth1 yet these drugs are still needlessly being prescribed for children. In 1982 over 75,000 prescriptions for a liquid tetracycline preparation were dispensed, most of which were probably for children; up to one third of paediatric patients have been affected,2–6 although the proportion has fallen over the last 10 years.7 Even a short course of tetracycline can stain both the permanent3,8 and deciduous teeth9 a disfiguring greyish-brown or yellow colour. Children are at risk from the 14th week in utero, when calcification of deciduous teeth begins, to their 7th year when calcification of the permanent teeth is complete. Whether tetracyclines produce enamel hypoplasia10 or promote caries11 is disputed.12

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