What are the areas needing Efficient Gene Delivery

Today an enormous amount of genetic information is available from databases, which are continuously fed by worldwide genome sequencing programs. Every day, the human genome-sequencing program alone provides new information about human genes with potential therapeutic value. On a diagnostic level, this will allow detecting “genetic defects” and also a prediction as to which amino acid in a given protein is concerned. However, unless the change in amino acids is meaningless or the malformed protein can be replaced, this information has limited therapeutic impact since curing the DNA defect is at present not possible. Another aspect concerns the large number of genes with unknown function. Since it is not possible to predict the three dimensional structure of a protein, let alone its biological function (interactions with other biological substances), from its amino acid sequence, the only way to “mine” the genetic information consists in a laborious transfection of a mammalian cell with the gene in question to enable said cell to produce the protein. Subsequently this allows studying the activity of the protein either directly within the cell or in vitro once enough of the material has been produced for further characterization.

The problem of quickly producing a certain amount of protein for further characterization and study is a major bottleneck in several areas of the life sciences and the related bioindustry. The list of sequenced genes for which the function of the corresponding protein is poorly understood is long. In addition, it is fairly easy to mutate genes in vitro, so a variety of new proteins can be encoded, some of which might have considerable therapeutic value. In contrast to the quick generation of new genes, the establishing of a stable recombinant production cell line requires at least a year for transfection, screening/amplification and scale up due to the difficulties of inserting the gene stably into a transcriptionally active region of the cell's chromosomal DNA. Recently, a much faster method -transient transfection - has been discussed as a means to produce quickly (within days) milligrams of a given protein. In this case, the foreign DNA is not inserted into the genome of the cell. The method, which until recently was only used for the production of smaller amounts of proteins through-out, had been shown to be compatible with at least the 1 L scale. If transfections could be established at the 100 liter scale or more, gram amounts of any protein could be produced within days. Screening of putative biopharmaceuticals but also basic research would profit enormously. Such large-scale transfections have not yet been achieved.

Gene therapy is another domain where efficient transfer of genes is essential. Many severe human diseases are caused by a genetic defect leading to the mal- or over-/ under-expression of the corresponding protein. Patients could be permanently cured if the missing genes could be transferred in a functional form into the concerned organs. Delivery of genes to specific tissues could become the most efficient medical treatment in the future, but for obvious reasons, the establishment of a very safe and well-controlled method for gene delivery is imperative.

Tags: Bio Technology, Bio Genetics, Gene Delivery

Related Posts by Categories