Gene synthesis
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Gene synthesis is the process of synthesizing an artificially designed gene into a physical DNA sequence.
Gene synthesis was first demonstrated by Har Gobind Khorana in 1970 for a short artificial gene. Nowadays, commercial gene synthesis services are available from hundreds of companies worldwide, with a price often below $1 a base pair. Some expressed concern that such services could be used by terrorists to create new strains of existing viruses/bacterias, or to resurrect extinct biological hazard organisms
[1].
Gene Optimization
While the ability to make increasingly long stretches of DNA efficiently and at lower prices is a technological driver of this field, increasingly attention is being focused on improving the design of genes for specific purposes. Early in the genome sequencing era, gene synthesis was used as an (expensive) source of cDNA's that were predicted by genomic or partial cDNA information but were difficult to clone. As higher quality sources of sequence verified cloned cDNA have become available, this practice has become less urgent. However, producing large amounts of protein from gene sequences (or at least the Protein coding regions of genes, the "Open Reading Frame" ORF) found in nature can sometimes prove difficult. Many of the most interesting proteins sought by molecular biologist are normally regulated to be expressed in very low amounts in wild type cells. Redesigning these genes offers a means to improve gene expression in many cases. Rewriting the open reading frame is possible because of the redundancy of the genetic code. Thus it is possible to change up to about a third of the nucleotides in an open reading frame and still produce the same protein. The available number of alternate designs possible for a given protein is astronomical. For a typical protein sequence of 300 amino acids there are over 10150 codon combinations that will encode an identical protein. Using optimization methods such as replacing rarely used codons with more common codons can have a dramatic effects. Further optimizations such as removing RNA secondary structures can also be included. Computer programs to written to perform these and other simultaneous optimizations are used to handle the enormous complexity of the task. A well optimized gene can improve protein expression 2 to 10 fold, and in some cases more than 100 fold improvements have been reported. Because of the large numbers of nucleotide changes made to the original DNA sequence, the only practical way to create the newly designed genes is to use gene synthesis.
[edit] See also
[edit] References
[edit] External links
Biodirectory
Mr. Gene - online gene synthesis provider
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