More on cloning

The difficulty of the task of isolating the desired recombinant from a population of transformed bacteria depends on the cloning strategy one adopts. Presently, there are three possible cloning methods; each has its own advantages and disadvantages. These are shotgun cloning, copy DNA (cDNA) cloning and direct gene sythesis. As to the methods of screening these recombinants, one could employ genetic methods, immunochemical methods and methods based on nucleic acid hybridization.

More often, the objective of cloning foreign proteins by recombinant DNA is a commercial product; it is then essential to maximize gene expression. This can be done by the following ways:

  • increase the number of copies of the plasmid vector per unit cell
  • use a stronger promoter to be able to synthesize more mRNA molecules
  • use the optimum sequnce of rbs and flanking DNA; a single base change can affect the translation by 1000-fold
  • proper choice of codon in the cloning gene
  • using highly stable recombinants which do not mutate to avoid loss of recombined DNA plasmids.
  • sythesize the proteins with the the appropriate protection from the reagents used

    Today, recombinant DNA technology has been applied extensively in the large scale production of proteins and enzymes that are of therapeutic and diagnostic interest. The most applied expression system is that of E. coli but a lot of research looks at animal and mamalian cell cultures because of certain limitations encountered in bacterial systems. Examples of important products of recombinant DNA technology are:

  • human insulin
  • human growth hormone
  • tissue plasminogen activator
  • factor viii
  • protein c
  • protein a
  • erythropoeitin

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