Question

You are a researcher at a small biotech company and your company has just obtained the license for use of a human GENOMIC DNA fragment putatively encoding a potentially novel protein, which is thought to regulate p53, the known tumor supressor protein. The scientists who originally cloned this GENE fragment HDM5 "claim" that HDM5 shares 93% DNA sequence homology with one of the HDM2 genes (refer to the review Levine & Oren, 2009). They propose that HDM5 may have HDM2-like properties and may be involved in regulating cell proliferation, and thus a good target to potentially develop as a cancer therapy. Your company has asked you to characterize the gene and gene products, as well as to provide an opinion as to its potential human therapeutic uses.

You are now convinced that the protein encoded by your HDM5 gene shares homology to HDM2 genes and shares functional similarities.

What is your advice to your company regarding the potential usefulness of this HDM5 gene and its product in the development of human therapies? Propose the mechanism of action of your gene's product and suggest one potential therapeutic approach based on this gene. (Consider consulting the Levine & Oren 2009 article!)

Answer 1

Before the advent of gene cloning technology, most genes were identified by the processes disrupted when the gene was mutated. This classical genetic approach—identifying the genes responsible for mutant phenotypes—is most easily performed in organisms that reproduce rapidly and are amenable to genetic manipulation, such as bacteria, yeasts, nematode worms, and fruit flies.

Once a gene has been identified, its function can often be predicted by identifying homologous genes whose functions are already known. When analyzing a newly sequenced genome, such a search serves as a first-pass attempt to assign functions to as many genes as possible, a process called annotation. Further genetic and biochemical studies are then performed to confirm whether the gene encodes a product with the predicted function.

Gene therapy is a way to fix a genetic problem at its source. With the new discovery of genes, and known properties it can be used for the treatment of genetic disorders. In the most straightforward cases, gene therapy adds a functional copy of a gene to cells that have only non-functional copies. .