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Large animal models of cardiovascular disease.

Tsang HG, Rashdan NA, Whitelaw CB, Corcoran BM, Summers KM, MacRae VE - Cell Biochem. Funct. (2016)

Bottom Line: In contrast, large animal models can show considerably greater similarity to humans.Furthermore, precise and efficient genome editing techniques enable the generation of tailored models for translational research.These novel systems provide a huge potential for large animal models to investigate the regulatory factors and molecular pathways that contribute to CVD in vivo.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, SCT, UK.

No MeSH data available.


Related in: MedlinePlus

TALEN or CRISPR/Cas9 systems of gene editing. After zygote injection of customized transcription activator‐like effector nuclease (TALEN) mRNA or Cas9 mRNA/single guide RNA (sgRNA), the gene of interest can be targeted and cut to produce a double strand break (DSB). TALENs work in pairs as the FokI endonuclease requires dimerization in order to produce a DSB. Various CRISPR/Cas9 systems exist for different applications. Fundamentally, the sgRNA directs the Cas9 nuclease to the site of targeting. After a DSB is created, DNA repair mechanisms occur via two main pathways: non‐homologous end joining (NHEJ) and homology directed repair (HDR). NHEJ leads to insertion/deletion mutations (indels), whilst HDR can be used to insert desired sequences. Through these mechanisms, an edited animal can be produced
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cbf3173-fig-0004: TALEN or CRISPR/Cas9 systems of gene editing. After zygote injection of customized transcription activator‐like effector nuclease (TALEN) mRNA or Cas9 mRNA/single guide RNA (sgRNA), the gene of interest can be targeted and cut to produce a double strand break (DSB). TALENs work in pairs as the FokI endonuclease requires dimerization in order to produce a DSB. Various CRISPR/Cas9 systems exist for different applications. Fundamentally, the sgRNA directs the Cas9 nuclease to the site of targeting. After a DSB is created, DNA repair mechanisms occur via two main pathways: non‐homologous end joining (NHEJ) and homology directed repair (HDR). NHEJ leads to insertion/deletion mutations (indels), whilst HDR can be used to insert desired sequences. Through these mechanisms, an edited animal can be produced

Mentions: A major goal in biological research is to further our understanding on the relationships between genotype and phenotype. Traditional approaches in understanding gene function have been restricted because of the lack of required tools for gene customization 273. More recently the possibilities of gene customization have expanded rapidly through the development of new and innovative technologies in the field of genome engineering, such as the use of zinc finger nucleases (ZFNs), transcription activator‐like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPRs). These next generation technologies serve as powerful tools for gene knock‐out and targeted manipulation of genomes (Figure 4).


Large animal models of cardiovascular disease.

Tsang HG, Rashdan NA, Whitelaw CB, Corcoran BM, Summers KM, MacRae VE - Cell Biochem. Funct. (2016)

TALEN or CRISPR/Cas9 systems of gene editing. After zygote injection of customized transcription activator‐like effector nuclease (TALEN) mRNA or Cas9 mRNA/single guide RNA (sgRNA), the gene of interest can be targeted and cut to produce a double strand break (DSB). TALENs work in pairs as the FokI endonuclease requires dimerization in order to produce a DSB. Various CRISPR/Cas9 systems exist for different applications. Fundamentally, the sgRNA directs the Cas9 nuclease to the site of targeting. After a DSB is created, DNA repair mechanisms occur via two main pathways: non‐homologous end joining (NHEJ) and homology directed repair (HDR). NHEJ leads to insertion/deletion mutations (indels), whilst HDR can be used to insert desired sequences. Through these mechanisms, an edited animal can be produced
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834612&req=5

cbf3173-fig-0004: TALEN or CRISPR/Cas9 systems of gene editing. After zygote injection of customized transcription activator‐like effector nuclease (TALEN) mRNA or Cas9 mRNA/single guide RNA (sgRNA), the gene of interest can be targeted and cut to produce a double strand break (DSB). TALENs work in pairs as the FokI endonuclease requires dimerization in order to produce a DSB. Various CRISPR/Cas9 systems exist for different applications. Fundamentally, the sgRNA directs the Cas9 nuclease to the site of targeting. After a DSB is created, DNA repair mechanisms occur via two main pathways: non‐homologous end joining (NHEJ) and homology directed repair (HDR). NHEJ leads to insertion/deletion mutations (indels), whilst HDR can be used to insert desired sequences. Through these mechanisms, an edited animal can be produced
Mentions: A major goal in biological research is to further our understanding on the relationships between genotype and phenotype. Traditional approaches in understanding gene function have been restricted because of the lack of required tools for gene customization 273. More recently the possibilities of gene customization have expanded rapidly through the development of new and innovative technologies in the field of genome engineering, such as the use of zinc finger nucleases (ZFNs), transcription activator‐like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPRs). These next generation technologies serve as powerful tools for gene knock‐out and targeted manipulation of genomes (Figure 4).

Bottom Line: In contrast, large animal models can show considerably greater similarity to humans.Furthermore, precise and efficient genome editing techniques enable the generation of tailored models for translational research.These novel systems provide a huge potential for large animal models to investigate the regulatory factors and molecular pathways that contribute to CVD in vivo.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, SCT, UK.

No MeSH data available.


Related in: MedlinePlus