Abstract

Sandeep Rajput, Sarvendra Dubey, Sanjana Ahirwar, Sakshi Sahu and Megha Shrivastava*

ABSTRACT

In spite of developments of neonatal intensive care medicine, it is still difficult or impossible to treat several inherited genetic disorders using conventional pharmacological methods. Gene therapy is a promising alternate approach for treating a variety of genetic disorders. By the time the patient reaches adulthood, however, it is often too late for effective treatment. But in several of these cases, neonatal gene therapy appears potentially useful against inherited disorders that are not obviously treatable through any other methods. Application of gene therapy to treat genetic and infectious diseases may have several advantages if performed in newborns. Because of the minimal adverse effect of the underlying disease on cells of the newborn, the relatively small size of infants, and the large amount of future growth, gene therapy may be more successful in newborns than in older children or adults. The presence of umbilical cord blood from newborns provides a unique and susceptible target for the genetic modification of hematopoietic stem cells. In our first trial of gene therapy in newborns, we inserted a normal adenosine deaminase gene into umbilical cord blood cells of three neonates with a congenital inunune deficiency. The trial demonstrated the successful transduction and engraftment of stem cells, which continue to contribute to leukocyte production more than 3 years later. A similar approach may be taken to insert genes that inhibit replication of H1V-l into umbifical cord blood cells of H1V-1-infected neonates. Many other metabolic and infectious disorders could be treated by gene therapy during the neonatal period if prenatal diagnoses are made and the appropriate techmcal and regulatory requirements have been met. This review describes the strategy for neonatal gene therapy for inherited disorders and presents preclinical neonatal gene therapy.