Gene therapy for the circumvention of inborn errors of metabolism (IEM) caused by single-nucleotide-polymorphisms (SNPs).
Single nucleotide polymorphisms (SNPs) are the result of point mutations in nuclear (and mitochondrial) DNA. Such localised damage to DNA (and its replicative mechanisms) may not be excised fully by the DNA repair mechanism in the genome: and therefore can become inheritable; subsequently to manifest later as an inborn error of metabolism (IEM). Causes of mutagenic damage to the DNA can include background radiation (such as emitted by radon gas), and by reactive oxygen species (ROS): and also by mutagenic chemicals that occur naturally (inter alia in the diet). Other causes of DNA damage are variable environmental hazards such as solar-derived short wave ultraviolet light A. Gene therapy involves the placement of missing genes into particular tissues by the harnessing of suitable vectors (originally these were animal viruses such as SV40). For example, gene therapy in the rat for diabetes has succeeded by liver-production of insulin (using genes obtained from pancreatic Islets of Langerhans cells). Many inborn errors of metabolism could be treated in this way: examples may include 100 haemoglobinopathies (such as sickle cell anaemia), phenylketonuria; and other diseases caused by lack of tissue-production of a particular enzyme (in its catalytically-active conformation).
Molecular Toxicology Group, School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
Alan
A
Wiseman
D003920:Diabetes Mellitus / Q000235:genetics / Q000628:therapy; D020022:Genetic Predisposition to Disease / Q000235:genetics* / Q000517:prevention & control*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000235:genetics* / Q000628:therapy*; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*