title: Polymer delivery systems for site-specific genome editing.
abstract: Triplex-forming peptide nucleic acids (PNAs) can be used to coordinate the recombination of short 50-60bp "donor DNA" fragments into genomic DNA, resulting in site-specific correction of genetic mutations or the introduction of advantageous genetic modifications. Site-specific gene editing in hematopoietic stem and progenitor cells (HSPCs) could result in the treatment or cure of inherited disorders of the blood such as β-thalassemia or sickle cell anemia. Gene editing in HSPCs and differentiated T cells could also help combat HIV infection by modifying the HIV co-receptor CCR5, which is necessary for R5-tropic HIV entry. However, translation of genome modification technologies to clinical practice is limited by challenges in intracellular delivery, especially in difficult-to-transfect hematolymphoid cells. Here, we review the use of engineered biodegradable polymer nanoparticles for site-specific genome editing in human hematopoietic cells, which represent a promising approach for ex vivo and in vivo gene therapy.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
authors.forename: Nicole Ali
authors.initials: NA
authors.lastname: McNeer
authors.forename: Erica B
authors.initials: EB
authors.lastname: Schleifman
authors.forename: Peter M
authors.initials: PM
authors.lastname: Glazer
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D016678:Genome; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D020135:Peptide Nucleic Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D011108:Polymers / Q000737:chemistry*; D052416:Targeted Gene Repair
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D020135:Peptide Nucleic Acids; D011108:Polymers; C051802:triplex DNA; D004247:DNA