Is the age of genetic surgery finally upon us?

Kmiec EB Surg Oncol 2015 Jun;24(2):95-9 PMID: 25936245 Abstract This review discusses gene editing and its potential in oncology. Gene editing has not evolved faster towards clinical application because of its difficulty in implementation. There have been many limitations of the tools thought to be useful in therapeutic gene editing. However, recently the combinatorial use

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The position of DNA cleavage by TALENs and cell synchronization influences the frequency of gene editing directed by single-stranded oligonucleotides

Rivera-Torres N, Strouse B, Bialk P, Niamat RA, Kmiec EB PLoS ONE 2014;9(5):e96483 PMID: 24788536 Abstract With recent technological advances that enable DNA cleavage at specific sites in the human genome, it may now be possible to reverse inborn errors, thereby correcting a mutation, at levels that could have an impact in a clinical setting.

Continue reading The position of DNA cleavage by TALENs and cell synchronization influences the frequency of gene editing directed by single-stranded oligonucleotides

Proliferation of genetically modified human cells on electrospun nanofiber scaffolds

Borjigin M, Strouse B, Niamat RA, Bialk P, Eskridge C, Xie J, Kmiec EB Mol Ther Nucleic Acids 2012 Dec;1:e59 PMID: 23212298 Abstract Gene editing is a process by which single base mutations can be corrected, in the context of the chromosome, using single-stranded oligodeoxynucleotides (ssODNs). The survival and proliferation of the corrected cells bearing

Continue reading Proliferation of genetically modified human cells on electrospun nanofiber scaffolds

DNA damage response pathway and replication fork stress during oligonucleotide directed gene editing

Bonner M, Strouse B, Applegate M, Livingston P, Kmiec EB Mol Ther Nucleic Acids 2012 Apr;1:e18 PMID: 23343929 Abstract Single-stranded DNA oligonucleotides (ODNs) can be used to direct the exchange of nucleotides in the genome of mammalian cells in a process known as gene editing. Once refined, gene editing should become a viable option for

Continue reading DNA damage response pathway and replication fork stress during oligonucleotide directed gene editing

Strand bias influences the mechanism of gene editing directed by single-stranded DNA oligonucleotides

Falgowski K, Falgowski C, York-Vickers C, Kmiec EB Nucleic Acids Res. 2011 Jun;39(11):4783-94 PMID: 21343181 Abstract Gene editing directed by modified single-stranded DNA oligonucleotides has been used to alter a single base pair in a variety of biological systems. It is likely that gene editing is facilitated by the direct incorporation of the oligonucleotides via

Continue reading Strand bias influences the mechanism of gene editing directed by single-stranded DNA oligonucleotides

DNA replication, cell cycle progression and the targeted gene repair reaction

Engstrom JU, Kmiec EB Cell Cycle 2008 May;7(10):1402-14 PMID: 18424915 Abstract Single-stranded oligonucleotides (ssODNs) can direct base changes in mammalian cells and influence changes in phenotype. The mechanism by which ssODNs alters the sequence is being revealed by studies carried out in model systems. In the long run, this information will provide the basis for

Continue reading DNA replication, cell cycle progression and the targeted gene repair reaction

Targeted gene repair activates Chk1 and Chk2 and stalls replication in corrected cells

Ferrara L, Kmiec EB DNA Repair (Amst.) 2006 Apr;5(4):422-31 PMID: 16414312 Abstract Oligonucleotides (ODNs) can direct the exchange of single nucleotides at specific sites in the mammalian genome. It is generally believed that the ODN aligns in homologous register with its complementary site in the target gene and provides a template for the endogenous repair

Continue reading Targeted gene repair activates Chk1 and Chk2 and stalls replication in corrected cells

Gene repair in mammalian cells is stimulated by the elongation of S phase and transient stalling of replication forks

Brachman EE, Kmiec EB DNA Repair (Amst.) 2005 Apr;4(4):445-57 PMID: 15725625 Abstract The repair of point mutations directed by modified single-stranded DNA oligonucleotides is dependent on the activity of proteins involved in homologous recombination (HR). As a consequence, factors that stimulate homologous recombination, such as double strand breaks, can impact the frequency with which repair

Continue reading Gene repair in mammalian cells is stimulated by the elongation of S phase and transient stalling of replication forks

Camptothecin enhances the frequency of oligonucleotide-directed gene repair in mammalian cells by inducing DNA damage and activating homologous recombination

Ferrara L, Kmiec EB Nucleic Acids Res. 2004;32(17):5239-48 PMID: 15466591 Abstract Camptothecin (CPT) is an anticancer drug that promotes DNA breakage at replication forks and the formation of lesions that activate the processes of homologous recombination (HR) and nonhomologous end joining. We have taken advantage of the CPT-induced damage response by coupling it to gene

Continue reading Camptothecin enhances the frequency of oligonucleotide-directed gene repair in mammalian cells by inducing DNA damage and activating homologous recombination