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Isogenic Human Disease Models
Isogenic human disease models are a family of cells that are selected or engineered to accurately model the genetics of a specific patient population, ''in vitro''. They are provided with a genetically matched 'normal cell' to provide an isogenic system to research disease biology and novel therapeutic agents. They can be used to model any disease with a genetic foundation. Cancer is one such disease for which isogenic human disease models have been widely used. Historical models Human isogenic disease models have been likened to 'patients in a test-tube', since they incorporate the latest research into human genetic diseases and do so without the difficulties and limitations involved in using non-human models. Historically, cells obtained from animals, typically mice, have been used to model cancer-related pathways. However, there are obvious limitations inherent in using animals for modelling genetically determined diseases in humans. Despite a large proportion of genetic conserv ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Genetics
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinians, Augustinian friar working in the 19th century in Brno, was the first to study genetics scientifically. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring over time. He observed that organisms (pea plants) inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene. Phenotypic trait, Trait inheritance and Molecular genetics, molecular inheritance mechanisms of genes are still primary principles of genetics in the 21st century, but modern genetics has expanded to study the function and behavior of genes. Gene structure and function, variation, and distribution are studied within the context of the Cell (bi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Adeno-associated Virus
Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus '' Dependoparvovirus'', which in turn belongs to the family ''Parvoviridae''. They are small (approximately 26 nm in diameter) replication-defective, nonenveloped viruses and have linear single-stranded DNA (ssDNA) genome of approximately 4.8 kilobases (kb). Several features make AAV an attractive candidate for creating viral vectors for gene therapy, and for the creation of isogenic human disease models. Gene therapy vectors using AAV can infect both dividing and quiescent cells and persist in an extrachromosomal state without integrating into the genome of the host cell. In the native virus, however, integration of virally carried genes into the host genome does occur. Integration can be important for certain applications, but can also have unwanted consequences. Recent human clinical trials using AAV for gene therapy in the retina have shown ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Genetics Experiments
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar working in the 19th century in Brno, was the first to study genetics scientifically. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring over time. He observed that organisms (pea plants) inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene. Trait inheritance and molecular inheritance mechanisms of genes are still primary principles of genetics in the 21st century, but modern genetics has expanded to study the function and behavior of genes. Gene structure and function, variation, and distribution are studied within the context of the cell, the organism (e.g. dominance), and within the cont ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Genetic Engineering
Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of Genetic engineering techniques, technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by Artificial gene synthesis, artificially synthesising the DNA. A Vector (molecular biology), construct is usually created and used to insert this DNA into the host organism. The first recombinant DNA molecule was made by Paul Berg in 1972 by combining DNA from the monkey virus SV40 with the Lambda phage, lambda virus. As well as inserting genes, the process can be used to remove, or "Gene knockout, knock out", genes. The new DNA can either be inserted randomly or Gene targeting, targeted to a spe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Human Genetics
Human genetics is the study of inheritance as it occurs in Human, human beings. Human genetics encompasses a variety of overlapping fields including: classical genetics, cytogenetics, molecular genetics, biochemical genetics, genomics, population genetics, developmental genetics, clinical genetics, and genetic counseling. Genes are the common factor of the qualities of most human-inherited traits. Study of human genetics can answer questions about human nature, can help understand diseases and the development of effective treatment and help us to understand the genetics of human life. This article describes only basic features of human genetics; for the genetics of disorders please see: medical genetics. For information on the genetics of DNA repair defects related to accelerated aging and/or increased risk of cancer please see: DNA repair-deficiency disorder. Genetic differences and inheritance patterns Inheritance of traits for humans are based upon Gregor Mendel's model ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Synthetic Lethality
Synthetic lethality is defined as a type of genetic interaction where the combination of two genetic events results in cell death or death of an organism. Although the foregoing explanation is wider than this, it is common when referring to synthetic lethality to mean the situation arising by virtue of a combination of deficiencies of two or more genes leading to cell death (whether by means of apoptosis or otherwise), whereas a deficiency of only one of these genes does not. In a synthetic lethal genetic screen, it is necessary to begin with a mutation that does not result in cell death, although the effect of that mutation could result in a differing phenotype (slow growth for example), and then systematically test other mutations at additional loci to determine which, in combination with the first mutation, causes cell death arising by way of deficiency or abolition of expression. Synthetic lethality has utility for purposes of molecular targeted cancer therapy. The first exampl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Recombinant AAV Mediated Genome Engineering
Recombinant adeno-associated virus (rAAV) based genome engineering is a genome editing platform centered on the use of recombinant AAV vectors that enables insertion, deletion or substitution of DNA sequences into the genomes of live mammalian cells. The technique builds on Mario Capecchi and Oliver Smithies' Nobel Prize–winning discovery that homologous recombination (HR), a natural hi-fidelity DNA repair mechanism, can be harnessed to perform precise genome alterations in mice. rAAV mediated genome-editing improves the efficiency of this technique to permit genome engineering in any pre-established and differentiated human cell line, which, in contrast to mouse ES cells, have low rates of HR. The technique has been widely adopted for use in engineering human cell lines to generate isogenic human disease models. It has also been used to optimize bioproducer cell lines for the biomanufacturing of protein vaccines and therapeutics. In addition, due to the non-pathogenic nature of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria and archaea; however plasmids are sometimes present in and eukaryotic organisms as well. Plasmids often carry useful genes, such as those involved in antibiotic resistance, virulence, secondary metabolism and bioremediation. While chromosomes are large and contain all the essential genetic information for living under normal conditions, plasmids are usually very small and contain additional genes for special circumstances. Artificial plasmids are widely used as vectors in molecular cloning, serving to drive the replication of recombinant DNA sequences within host organisms. In the laboratory, plasmids may be introduced into a cell via transformation. Synthetic plasmids are available for procurement over the internet by various vendors ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Homologous Recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organisms but may be also RNA in viruses). Homologous recombination is widely used by cells to accurately DNA repair, repair harmful DNA breaks that occur on both strands of DNA, known as double-strand breaks (DSB), in a process called homologous recombinational repair (HRR). Homologous recombination also produces new combinations of DNA sequences during meiosis, the process by which eukaryotes make gamete cells, like sperm and ovum, egg cells in animals. These new combinations of DNA represent genetic variation in offspring, which in turn enables populations to Adaptation, adapt during the course of evolution. Homologous recombination is also used in horizontal gene transfer to exchange genetic material between different strains and species ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Genome Engineering
Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly insert genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases (FokI and CRISPR associated protein, Cas), and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ). History Genome editing was pioneered in the 1990s, before the advent of the common current nuclease-based gene-editing platforms, but its use was limited by low efficiencies of editing. Genome editing with engineered nucleases, i.e. all three m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Zinc Finger Nuclease
Zinc-finger nucleases (ZFNs) are artificial restriction enzymes generated by fusing a zinc finger DNA-binding domain to a nuclease, DNA-cleavage domain. Zinc finger domains can be engineered to target specific desired DNA sequences and this enables zinc-finger nucleases to target unique sequences within complex genomes. By taking advantage of endogenous DNA repair machinery, these reagents can be used to precisely alter the genomes of higher organisms. Alongside CRISPR, CRISPR/Cas9 and TALEN, ZFN is a prominent tool in the field of genome editing. It was initially created by researcher Srinivasan Chandrasegaran. Domains DNA-binding domain The DNA-binding domains of individual ZFNs typically contain between three and six individual zinc finger repeats and can each recognize between 9 and 18 basepairs. If the zinc finger domains perfectly recognize a 3 basepair DNA sequence, they can generate a 3-finger array that can recognize a 9 basepair target site. Other procedures can u ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
In Vitro
''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, flasks, Petri dishes, and microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms; however, results obtained from ''in vitro'' experiments may not fully or accurately predict the effects on a whole organism. In contrast to ''in vitro'' experiments, ''in vivo'' studies are those conducted in living organisms, including humans, known as clinical trials, and whole plants. Definition ''In vitro'' (Latin language, Latin for "in glass"; often not italicized in English usage) studies are conducted ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
