Vector-Mediated Genotoxicity and Mutagenicity in Hematopoietic Stem Cell Gene Therapy
Comprehensive Hematology and Stem Cell Research: Volume 1-5, Elsevier, 2024
- Yayın Türü: Kitapta Bölüm / Araştırma Kitabı
- Basım Tarihi: 2024
- Doi Numarası: 10.1016/b978-0-443-15717-2.00100-1
- Yayınevi: Elsevier
- Anahtar Kelimeler: Genetic diseases, Genotoxicity, Hematopoietic stem cell gene therapy, Mutagenicity, Viral vector
- Kırklareli Üniversitesi Adresli: Evet
Özet
Hematopoiesis is the production of all cellular components of blood and continues throughout life. Diseases of the hematopoietic system can profoundly affect human life. Most of the inherited blood cell diseases can be treated by transplantation of allogeneic hematopoietic stem cells (HSCs). Genetic modification of HSCs provides tremendous potential for the treatment of hematopoietic genetic diseases. Gene therapy, with the help of a vehicle, is the correction of the genetic material that causes the cell dysfunction due to faulty genetic structure. Most of the inherited blood cell diseases including hemoglobinopathies, primary immune deficiencies, storage and metabolic disorders, stem cell defects, congenital cytopenias, familial haemophagocytic lymphohistiocytosis (FHL) and X-linked hyper-immunoglobulin M syndrome can be treated by transplantation of allogeneic hematopoietic stem cells (HSCs). Transplantation of genetically modified HSCs sometimes led to genotoxicity which resulted in leukemias and myelodysplastic syndromes in patients. Hence, the objectives of this chapter is to assess genotoxicity/mutagenicity of viral vectors and mitigation efforts in light of the most recent published results and to determine bottlenecks that impede the use of human gene therapy.