Neonatal gene therapy of glycogen storage disease type Ia using a feline immunodeficiency virus-based vector

Albert Grinshpun, Reba Condiotti*, Simon N. Waddington, Michael Peer, Eli Zeig, Sima Peretz, Alina Simerzin, Janice Chou, Chi Jiunn Pann, Hilla Giladi, Eithan Galun

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Glycogen storage disease type Ia (GSD-Ia), also known as von Gierke disease, is caused by a deficiency of glucose-6-phosphatase-α (G6Pase), a key enzyme in glucose homeostasis. From birth, affected individuals cannot maintain normal blood glucose levels and suffer from a variety of metabolic disorders, leading to life-threatening complications. Gene therapy has been proposed as a possible option for treatment of this illness. Vectors have been constructed from feline immunodeficiency virus (FIV), a nonprimate lentivirus, because the wild-type virus does not cause disease in humans. Previously, we have shown that these vectors are capable of integrating stably into hepatocyte cell lines and adult murine livers and lead to long-term transgene expression. In the current work, we have assessed the ability to attenuate disease symptoms in a murine model of GSD-Ia. Single administration of FIV vectors containing the human G6Pase gene to G6Pase-α -/- mice did not change the biochemical and pathological phenotype. However, a double neonatal administration protocol led to normalized blood glucose levels, significantly extended survival, improved body weight, and decreased accumulation of liver glycogen associated with the disease. This approach shows a promising paradigm for treating GSD-Ia patients early in life thereby avoiding long-term consequences.

Original languageAmerican English
Pages (from-to)1592-1598
Number of pages7
JournalMolecular Therapy
Issue number9
StatePublished - Sep 2010
Externally publishedYes

Bibliographical note

Funding Information:
We thank the Children’s Fund for Glycogen Storage Disease Research, and Alfy and Lilyan Nathan for financially supporting this work.


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