scholarly journals Human Gene Targeting Favors Insertions Over Deletions

2008 ◽  
Vol 19 (9) ◽  
pp. 907-914 ◽  
Author(s):  
David W. Russell ◽  
Roli K. Hirata
Keyword(s):  
Gene Targeting ◽  
Human Gene

Construction of chicken × human microcell hybrids for human gene targeting

1997 ◽  
Vol 76 (1-2) ◽  
pp. 72-76 ◽  
Author(s):  
M. Koi ◽  
P.W. Lamb ◽  
L. Filatov ◽  
A.P. Feinberg ◽  
J.C. Barrett
Keyword(s):  
Gene Targeting ◽  
Human Gene ◽  
Microcell Hybrids

scholarly journals Efficient RNP-directed Human Gene Targeting Reveals SPDEF Is Required for IL-13–induced Mucostasis

2020 ◽  
Vol 62 (3) ◽  
pp. 373-381 ◽  
Author(s):  
Kyung Duk Koh ◽  
Sana Siddiqui ◽  
Dan Cheng ◽  
Luke R. Bonser ◽  
Dingyuan I. Sun ◽  
...  
Keyword(s):  
Gene Targeting ◽  
Human Gene

scholarly journals Human Gene Targeting by Adeno-Associated Virus Vectors Is Enhanced by DNA Double-Strand Breaks

2003 ◽  
Vol 23 (10) ◽  
pp. 3550-3557 ◽  
Author(s):  
Daniel G. Miller ◽  
Lisa M. Petek ◽  
David W. Russell
Keyword(s):  
Gene Targeting ◽  
Human Gene ◽  
Retroviral Vectors ◽  
Strand Break ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Adeno Associated Virus ◽  
Strand Breaks ◽  
Double Stranded Dna ◽  
Linear Molecules

ABSTRACT The use of adeno-associated virus (AAV) to package gene-targeting vectors as single-stranded linear molecules has led to significant improvements in mammalian gene-targeting frequencies. However, the molecular basis for the high targeting frequencies obtained is poorly understood, and there could be important mechanistic differences between AAV-mediated gene targeting and conventional gene targeting with transfected double-stranded DNA constructs. Conventional gene targeting is thought to occur by the double-strand break (DSB) model of homologous recombination, as this can explain the higher targeting frequencies observed when DSBs are present in the targeting construct or target locus. Here we compare AAV-mediated gene-targeting frequencies in the presence and absence of induced target site DSBs. Retroviral vectors were used to introduce a mutant lacZ gene containing an I-SceI cleavage site and to efficiently deliver the I-SceI endonuclease, allowing us to carry out these studies with normal and transformed human cells. Creation of DSBs by I-SceI increased AAV-mediated gene-targeting frequencies 60- to 100-fold and resulted in a precise correction of the mutant lacZ reporter gene. These experiments demonstrate that AAV-mediated gene targeting can result in repair of a DNA DSB and that this form of gene targeting exhibits fundamental similarities to conventional gene targeting. In addition, our findings suggest that the selective creation of DSBs by using viral delivery systems can increase gene-targeting frequencies in scientific and therapeutic applications.

scholarly journals Use of double-replacement gene targeting to replace the murine alpha-lactalbumin gene with its human counterpart in embryonic stem cells and mice.

1994 ◽  
Vol 14 (2) ◽  
pp. 1009-1016 ◽  
Author(s):  
A Stacey ◽  
A Schnieke ◽  
J McWhir ◽  
J Cooper ◽  
A Colman ◽  
...  
Keyword(s):  
Gene Targeting ◽  
Germ Line ◽  
Human Gene ◽  
Es Cells ◽  
Embryonic Stem ◽  
Second Step ◽  
Null Mutation ◽  
Selection System ◽  
Human Counterpart ◽  
Alpha Lactalbumin

The mouse alpha-lactalbumin gene has been replaced with the human gene by two consecutive rounds of gene targeting in hypoxanthine phosphoribosyltransferase (HPRT)-deficient feeder-independent murine embryonic stem (ES) cells. One mouse alpha-lactalbumin allele was first replaced by an HPRT minigene which was in turn replaced by human alpha-lactalbumin. The end result is a clean exchange of defined DNA fragments with no other DNA remaining at the target locus. Targeted ES cells at each stage remained capable of contributing efficiently to the germ line of chimeric animals. Double replacement using HPRT-deficient ES cells and the HPRT selection system is therefore a powerful and flexible method of targeting specific alterations to animal genes. A typical strategy for future use would be to generate a null mutation which could then be used to produce multiple second-step alterations at the same locus.

scholarly journals A genome-wide map of adeno-associated virus–mediated human gene targeting

2014 ◽  
Vol 21 (11) ◽  
pp. 969-975 ◽  
Author(s):  
David R Deyle ◽  
R Scott Hansen ◽  
Anda M Cornea ◽  
Li B Li ◽  
Amber A Burt ◽  
...  
Keyword(s):  
Gene Targeting ◽  
Human Gene ◽  
Adeno Associated Virus ◽  
Genome Wide ◽  
A Genome

scholarly journals The effects of polymorphisms on human gene targeting

2013 ◽  
Vol 42 (5) ◽  
pp. 3119-3124 ◽  
Author(s):  
David R. Deyle ◽  
Li B. Li ◽  
Gaoying Ren ◽  
David W. Russell
Keyword(s):  
Gene Targeting ◽  
Base Pair ◽  
Human Gene ◽  
Human Cells ◽  
Specific Targeting ◽  
Mismatched Base Pair ◽  
Allele Specific ◽  
Dna Mismatches ◽  
Target Sequences

AbstractDNA mismatches that occur between vector homology arms and chromosomal target sequences reduce gene targeting frequencies in several species; however, this has not been reported in human cells. Here we demonstrate that even a single mismatched base pair can significantly decrease human gene targeting frequencies. In addition, we show that homology arm polymorphisms can be used to direct allele-specific targeting or to improve unfavorable vector designs that introduce deletions.

scholarly journals Human Gene Targeting Favors Insertions Over Deletions

2008 ◽  
Vol 0 (ja) ◽  
pp. 081015093227032
Author(s):  
David Russell ◽  
Roli Hirata
Keyword(s):  
Gene Targeting ◽  
Human Gene

scholarly journals Human gene targeting by viral vectors

1998 ◽  
Vol 18 (4) ◽  
pp. 325-330 ◽  
Author(s):  
David W. Russell ◽  
Roll K. Hirata
Keyword(s):  
Gene Targeting ◽  
Viral Vectors ◽  
Human Gene
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