Work

In vivo genome editing shows promise for treating pulmonary diseases

Year: 2023

Type: article

Abstract: Surfactant protein B (SP-B) is crucial for maintaining lung surfactant homeostasis and facilitating alveolar expansion and contraction during breathing. 1 Weaver T.E. Conkright J.J. Function of surfactant proteins B and C. Annu. Rev. Physiol. 2001; 63: 555-578 Crossref PubMed Scopus (317) Google Scholar SP-B deficiency results from autosomal recessive loss-of-function mutation(s) in the SFTPB gene. Infants born with SP-B deficiency experience severe breathing difficulties, leading to fatal respiratory distress within the first few months of life. 2 Nogee L.M. Wert S.E. Proffit S.A. Hull W.M. Whitsett J.A. Allelic heterogeneity in hereditary surfactant protein B (SP-B) deficiency. Am. J. Respir. Crit. Care Med. 2000; 161: 973-981 Crossref PubMed Scopus (213) Google Scholar While the incidence of SP-B deficiency is rare (1 in 1 million live births), 3 Cole F.S. Hamvas A. Rubinstein P. King E. Trusgnich M. Nogee L.M. deMello D.E. Colten H.R. Population-based estimates of surfactant protein B deficiency. Pediatrics. 2000; 105: 538-541 Crossref PubMed Google Scholar it can currently only be treated through lung transplantation, but suitable donors are scarce. 4 Eldridge W.B. Zhang Q. Faro A. Sweet S.C. Eghtesady P. Hamvas A. Cole F.S. Wambach J.A. Outcomes of Lung Transplantation for Infants and Children with Genetic Disorders of Surfactant Metabolism. J. Pediatr. 2017; 184: 157-164.e2 Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar SP-B is synthesized and secreted by alveolar type II (ATII) cells, yet patients do not respond to exogenous surfactant treatments. Therefore, gene therapy is being considered as a potential approach for treating this disease 5 Cooney A.L. Wambach J.A. Sinn P.L. McCray Jr., P.B. Gene Therapy Potential for Genetic Disorders of Surfactant Dysfunction. Front. Genome Ed. 2021; 3: 785829 Crossref PubMed Scopus (13) Google Scholar ,6 Alapati D. Morrisey E.E. Gene Editing and Genetic Lung Disease. Basic Research Meets Therapeutic Application. Am. J. Respir. Cell Mol. Biol. 2017; 56: 283-290 Crossref PubMed Scopus (29) Google Scholar and has been assessed in SP-B conditional knockout mice.

Source: Molecular Therapy

DOI: 10.1016/j.ymthe.2023.11.004

Author: Ziying Yan

Institution: University of Iowa

Language: English

Topic: Neonatal Respiratory Health Research

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,900