Related Experiment Video
Updated: Jun 12, 2026
Lentiviral Vector-mediated Gene Therapy of Hepatocytes Ex Vivo for Autologous Transplantation in Swine
Published on: November 4, 2018
Neonatal gene therapy of glycogen storage disease type Ia using a feline immunodeficiency virus-based vector
Albert Grinshpun1, Reba Condiotti, Simon N Waddington
1Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Insights
Gene therapy using feline immunodeficiency virus (FIV) vectors shows promise for Glycogen storage disease type Ia (GSD-Ia). A double neonatal administration of G6Pase gene vectors normalized blood glucose and extended survival in a mouse model.
Area of Science:
- Biochemistry
- Genetics
- Gene Therapy
Background:
- Glycogen storage disease type Ia (GSD-Ia), or von Gierke disease, results from glucose-6-phosphatase-alpha (G6Pase) deficiency, impairing glucose homeostasis.
- Affected individuals experience severe metabolic disorders and life-threatening complications from birth due to inability to maintain blood glucose levels.
Purpose of the Study:
- To evaluate the efficacy of feline immunodeficiency virus (FIV) vectors for treating GSD-Ia in a murine model.
- To assess if gene therapy can attenuate disease symptoms and improve outcomes in GSD-Ia.
Main Methods:
- Construction of FIV vectors carrying the human G6Pase gene.
- Administration of FIV vectors to G6Pase-alpha(-/-) mice, comparing single and double neonatal dosing protocols.
- Assessment of biochemical and pathological phenotypes, including blood glucose levels, body weight, liver glycogen accumulation, and survival rates.
Main Results:
- A single administration of FIV vectors did not alter the disease phenotype in GSD-Ia mice.
- A double neonatal administration protocol resulted in normalized blood glucose levels.
- This protocol significantly extended survival, improved body weight, and reduced liver glycogen accumulation in the GSD-Ia mouse model.
Conclusions:
- Early and repeated gene therapy with FIV vectors shows potential for treating GSD-Ia.
- Neonatal administration of G6Pase gene therapy offers a promising strategy to prevent long-term complications of GSD-Ia.
Abstract:
Glycogen storage disease type Ia (GSD-Ia), also known as von Gierke disease, is caused by a deficiency of glucose-6-phosphatase-alpha (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-alpha(-/-) 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.
Related Concept Videos
00:59Gene Therapy
00:59Gene Therapy