Structural Biochemistry/DNA recombinant techniques/Designer Genes

The Modern Approach to Gene Design
A typical gene design cycle starts with defining a desired target protein. From there the scientist, using a gene composer computer program, inputs information such as functional characterization data, sequence alignments or knowledge of related 3D structural information from various sources that pertain to the desired protein. Secondary structural information is annotated and amino acids in the active domains (i.e. - participate in ligand binding sites, are water exposed, or form crystal contacts) are labeled, and multiple amino acid sequence variants are generated. The next step is back-translating designed amino acid sequences into nucleic acid sequences. The program will generate optimized nucleic acid sequences based on defined criteria input by the user, such as codon optimization for highly expressed proteins, suppressing strong mRNA structure forming elements and avoiding undesired restriction sites. Finally, sequences for complete genes are output. The adoption of this new method of protein design allows heterologous expression of proteins to be tested more quickly and minimizes failure rates.

Benefits/Uses of Gene Design
Gene/Protein design is currently being utilized for a number of important applications including:

1. Immunotoxins- chimeric protein made from a gene for an antibody and a gene for a toxin, which can be used to kill cells that are recognized by the antibody

2. Synthetic vaccines- recombining DNA to create noninfectious coat proteins of viruses

3. Completely new genes and proteins with functions not found in nature

4. New enzymes

5. New drugs

6. Disease research for Malaria, Anthrax, HIV, Alzheimer's and Various Cancers