Protein-coding Genes
The concept of gene therapy refers to a vast series of applications, both in vitro and in vivo, with the utilization of nucleic acids for therapeutic intentions. As introduced, there is no lack of data and information on the structure of human genomes in the last. When the first draft of the human genome sequence published in 2001, there were approximately 30,000-40,000 protein-coding sequences. Estimates of the current updates are closer to 20,000 protein-coding genes, as well as an expanding number of functional, non-coding RNA sequences. To date, identifying the molecular basis of inherited genetic disorders has become extremely easier. Meanwhile, scientists have achieved the identification of 3674 human phenotypes, the majority of which are single-gene mutations.
Gene Therapy
Table.1 Therapeutic nucleic acids. (Giacca, 2010)
Originally, the term gene therapy has been developed with the idea of providing a missing cellular function by transferring a normal copy of a modified or altered gene into the recipient cells. Indeed, in human cells, the average size of protein-coding genes, with an estimate of 27 kb, is by far longer than the maximum length fitting the most common gene delivery systems. For this reason, gene therapy is often generally based on the transfer of cDNAs or of their protein-coding portion. The cDNAs are a class of double-stranded (ds) DNA copies derived from the gene mRNAs, with an average length of ~2.5 kb. And their corresponding protein-coding potion has an average length of ~1.5 kb, equivalently to about 500 codons.
One report has described analytically the multiple types of small molecules that are part of gene therapy. They 're diverse nucleic acids having a possible therapeutic function and can be sorted into one of two classes:
- DNA sequences coding for proteins with varieties of cellular functions;
- Nucleic acids, including DNAs and RNAs, with regulatory function, either generated as synthetic molecules or, in the case of RNAs, expressed inside the cells after transcription of the corresponding gene.
Protein-coding Genes
The genome sequence is a blueprint of organisms, the set of instructions explaining its biological traits. The unfolding of these instructions is launched by the transcription of DNA into RNA sequences. Based on the standard model, the majority of RNA sequences stem from protein-coding genes, namely, they're processed into mRNAs after their export to the cytosol, and are translated into certain proteins.
In the view of the molecular point, transferring a gene, or its cDNA or cDNA coding portion has substantially different properties. Both cDNAs and their coding parts require to be transcribed from promoters that are commonly different from the natural ones, which are usually too large to be used. Additionally, the cDNA coding regions alone lack the regulatory elements controlling gene expression at the post-transcriptional level, which are usually located in the introns or the untranslated regions (UTRs) at the 3' and the 5' ends of cDNAs. Normally, these portions participate in the regulation of cDNA transport, stability, subcellular localization, and translation of cellular mRNAs. However, on the other hand, in several contexts, the levels at which proteins are produced are not very important, and thus a tight translational or post-translational regulation of gene expression is not necessary. For instance, this is the case of proteins replacing missing cellular functions in the hereditary diseases of metabolism, or antigens for secreted antibodies or anticancer vaccination. In these mentioned cases, the transfer of protein-coding regions under the regulation of a strong promoter, such as the promoter element for the cytomegalovirus (CMV) immediate-early genes, is adequate. In some situations, the inclusion of a small intron upstream of the cDNA coding sequence or a 3' UTR downstream of it, has been known to improve the expression of the protein of interest.
Protein-coding Genes Related Studies
The proteins encoded by therapeutic genes have very different functions and activities, ranging from the substitution of a missing cellular protein to the modulation of immune systems. At Creative Biolabs, we not only focus on gene therapy solutions that contribute to accelerating challenging projects but pay attention to the study of many different potential therapeutic nucleic acids, for example, RNAi technology.
Reference
- Giacca, M. (2010). Therapeutic nucleic acids. Gene Therapy. Chaper2: 9-45.
