Methods for the reduction or ablation of gene function

  • Matthew G. F. Sharp
  • John J. Mullins


The ability to reduce the expression of specific genes by inhibiting their expression directly or by interfering with the gene product is desirable for both therapeutic and experimental reasons. With advances in gene therapy, strategies are being developed to replace defective genes or introduce exogenous inhibitors of gene expression such as antisense RNAs or ribozyme sequences, which are targeted at specific messenger (m)RNAs. In basic biomedical research, gene knockout techniques and antisense RNAs are being used experimentally to gain further understanding of developmental and physiologi­cal processes and to identify the function of specific genes. These approaches allow the investigation of individual genes in the context of a complex living organism, and can identify a causal relationship between a particular gene mutation and a disease phenotype. The methodologies appropriate for the experimental manipulation of gene expression in living organisms can be divided broadly into two categories: (a) gene targeting, whereby a gene is modified by the integration of a homologous DNA construct, such that the endogenous gene is no longer able to give rise to a functional, stable mRNA and (b) the reduction in, or loss of, the function of a geneproduct, which can be achieved via various antisense inhibition strategies, the introduction of point mutations, or the expression of dominantly-acting mutated proteins


Cystic Fibrosis Embryonic Stem Cell Selectable Marker Internal Ribosome Entry Site Mouse Embryonic Stem Cell 
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© Rapid Science Publishers 1996

Authors and Affiliations

  • Matthew G. F. Sharp
  • John J. Mullins

There are no affiliations available

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