Zinc finger nuclease technology: Advances and obstacles in modelling and treating genetic disorders

Jabalameli, Hamid Reza; Zahednasab, Hamid; Karimi-Moghaddam, Amin; Jabalameli, M. Reza

doi:10.1016/j.gene.2014.12.044

Cited by 29 publications

(19 citation statements)

References 55 publications

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“…The paradigm has shifted to one in which the mutations initially found in humans are modeled by design in mice. With the advent of a new generation of genome editing tools (Wijshake et al, 2014) such as zinc-finger nucleases (Chou et al, 2012; Jabalameli et al, 2015; Overlack et al, 2012; Pittler et al, 2013; Sandoval, 2012; Sasson and Kelleher, 2014), the CRISPR/Cas9 system (Pelletier et al, 2015; Sander and Joung, 2014), and TALENS (Sommer et al, 2015) (transcriptional activator-like effector nucleases), the generation of such animals is becoming even more efficient. An important use of existing and new animal models is to apply structural methods, as well as biochemical and physiological analyses, to gain insights into structural and functional consequences of mutations, and to understand mechanisms of cell death.…”

Section: Genetic Approaches To Understanding the Molecular Basis Omentioning

confidence: 99%

Structural and molecular bases of rod photoreceptor morphogenesis and disease

Wensel

Zhang

Anastassov

et al. 2016

Progress in Retinal and Eye Research

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The rod cell has an extraordinarily specialized structure that allows it to carry out its unique function of detecting individual photons of light. Both the structural features of the rod and the metabolic processes required for highly amplified light detection seem to have rendered the rod especially sensitive to structural and metabolic defects, so that a large number of gene defects are primarily associated with rod cell death and give rise to blinding retinal dystrophies. The structures of the rod, especially those of the sensory cilium known as the outer segment, have been the subject of structural, biochemical, and genetic analysis for many years, but the molecular bases for rod morphogenesis and for cell death in rod dystrophies are still poorly understood. Recent developments in imaging technology, such as cryo-electron tomography and super-resolution fluorescence microscopy, in gene sequencing technology, and in gene editing technology are rapidly leading to new breakthroughs in our understanding of these questions. A summary is presented of our current understanding of selected aspects of these questions, highlighting areas of uncertainty and contention as well as recent discoveries that provide new insights. Examples of structural data from emerging imaging technologies are presented.

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Section: Genetic Approaches To Understanding the Molecular Basis Omentioning

confidence: 99%

Structural and molecular bases of rod photoreceptor morphogenesis and disease

Wensel

Zhang

Anastassov

et al. 2016

Progress in Retinal and Eye Research

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“…The elucidation of the zinc finger protein structure and the mechanism by which zinc finger proteins target a particular DNA sequence transformed the early field of genetic engineering, allowing specific DNA sequences of choice to be modified [15,16]. The first proof of principle of this technique in humans was applied to X-linked severe combined immune deficiency (SCID) in which fusion of zinc finger proteins to a nuclease domain caused a double stranded break creating a specific DNA sequence alteration stimulating homologous recombination between the chromosome and an extrachromosomal DNA donor [17].…”

Section: Discussionmentioning

confidence: 99%

Cortical gene expression: prognostic value for seizure outcome following temporal lobectomy and amygdalohippocampectomy

et al. 2016

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Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between epilepsy patients rendered seizure-free versus non-seizure-free following anterior temporal lobectomy with amygdalohippocampectomy (ATL/AH). Twenty four patients underwent ATL/AH to treat medically intractable seizures of temporal lobe origin (mean age 35.5 years, mean follow up 42.2 months), they were then dichotomized into seizure-free and non-seizure-free groups. Tissue RNA was isolated from the lateral temporal cortex and gene expression analysis was performed. Whole genome data were analyzed for prognostic value for seizure-free outcome following ATL/AH by logistic regression. Genes that could distinguish seizure outcome groups were identified based on providing an accuracy of >0.90 judging by area under the receiver operating characteristic curve, AUC, with a P value of the slope coefficient of <0.05. Four genes and seven RNA probes were with prognostic value for post-operative seizure-free outcome. Gene expression associated with seizure-free outcome included relative down-regulation of: zinc finger protein 852 (ZNF852); CUB domain containing protein 2 (CDCP2); proline-rich transmembrane protein 1 (PRRT1); hypothetical LOC440200 (FLJ41170); RNA probe 8047763; RNA probe 8126238; RNA probe 8113489; RNA probe 8092883; RNA probe 7935228; RNA probe 806293 and RNA probe 8104131. This study describes the predictive value of temporal cortical gene expression for seizure-free outcome after ATL/AH. Four genes and seven RNA probes were found to predict post-operative seizure-free outcome. Future prospective investigation of these genes and probes in human brain tissue and blood could establish new biomarkers predictive of seizure outcome following ATL/AH.

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“…The other class of the designed enzymes includes modified versions of native proteins constructed either by introducing mutations through molecular design or directed evolution methods or by creating chimera from independent catalytic and DNA binding domains. The main strategies applied in these experiments on artificial meganucleases constructed from homing endonucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) with associated nucleases (Cas) were discussed in several recent reviews [26][27][28][29][30][31][32][33].…”

Section: Current Artificial Nucleasesmentioning

confidence: 99%

Rescue of the activity of HNH nuclease mutants - towards controlled enzymes for gene therapy

Gyurcsik

2016

CPPS

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Artificial nucleases are designed for in vivo gene engineering, as the DNA cleavage performed at a specific target site enhances the effectiveness of the cell's DNA repair machinery. The therapeutic potential of the above phenomenon stems from the knowledge that (i) the shifted reading frame can be restored by non-homologous end-joining, or (ii) a DNA of erroneous sequence -causing a genetic disease -can be corrected by homologous recombination in the presence of a suitable DNA template. Besides the advantageous properties of the nowadays applied zinc finger nucleases, TALE nucleases and the CRISPR/Cas9 system, they possess a residual citotoxicity. This is related to offtarget cleavages, which could be prevented by the strict regulation of the enzymes. The studies on enzymes acting naturally in a controlled manner are beneficial to get better insight into their mechanism. Such enzymes or their appropriate domains may be the most promising alternatives to the presently applied ones. As an example, the DNA cleavage of the inactive HNH nuclease mutants is inducible in a multiple way. This property may be used for establishing a control mechanism and thus, in combination with specific DNA-binding domains they are good candidates for the catalytic site of artificial nucleases. Here we collect the results on the properties of the HNH nucleases that allow for their redesign into enzymes with possible therapeutic applications.

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Zinc finger nuclease technology: Advances and obstacles in modelling and treating genetic disorders

Cited by 29 publications

References 55 publications

Structural and molecular bases of rod photoreceptor morphogenesis and disease

Structural and molecular bases of rod photoreceptor morphogenesis and disease

Cortical gene expression: prognostic value for seizure outcome following temporal lobectomy and amygdalohippocampectomy

Rescue of the activity of HNH nuclease mutants - towards controlled enzymes for gene therapy

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