Understanding the role of DNA in biology is arguably the single most important scientific advance of the 20th century. It provides the molecular basis of inheritance, and understanding how the genetic code is translated into proteins providing a whole new insight into the workings of the human body.
The fundamental unit of inheritance is the gene, a stretch of DNA that contains the information needed to make one protein. It soon became clear that errors in the DNA sequence of a single gene caused a vast array of inherited diseases, such as cystic fibrosis and Duchene Muscular Dystrophy.
Through the latter decades of the 20th Century, advances in the methodology for sequencing DNA accelerated the pace of discovery, culminating in the publication of the first complete human genome sequence (that is, the sequence of all the DNA in a cell) at the turn of the millennium. This new molecular genetics identified literally thousands of genetic mutations that caused human diseases.
Even today, the ripples of the genomics revolution are still playing out. We are seeing the first gene therapies approved as medicines, where individuals with a mutant copy of a particular gene are provided with additional normal copies, allowing the correct protein now to be made, in many cases with impressive benefits.
In haemophilia A, which causes bleeding, mutations in the DNA of the gene that encodes a protein called Factor VIII important for normal clotting. Once the genetic basis for this deficiency was understood in the 1980s, scientists at Genentech were able to clone the normal copy of the gene and insert it into cultured cells so they could make Factor VIII, which could be purified and injected into patients with haemophilia A, effectively curing them.
The obvious next step (to put the normal copy of the gene into the patient directly), however, has taken thirty more years, as the serious technical challenges of introducing new DNA sequences into a living person were gradually overcome. But today it is a reality, and several companies are racing to the FDA for approval of a “once and done” treatment, giving patients a normal copy of the gene so they can, for the first time, produce their own Factor VIII.
Even that is not the end of the journey. With the discovery of CRISPR, biologists can edit faulty genes directly. The next generation of tools promise DNA editing as easy as installing new software.
In the face of such impressive progress, it is not surprising that the role of DNA in biology has come to be seen as central. Reading its sequence identifies the causes of disease, and correcting any sequence errors cures the patient. Even the language of …
RxCelerate Ltd is an outsourced drug development platform based near Cambridge, UK. We specialize in delivering an entire road map of drug development services from discovery and medicinal chemistry through to formal preclinical development and clinical up to Phase IIa. In the last five years, we have witnessed dramatic changes in the drug development …