Source:
Generated By: https://synbiohub.org/public/igem/igem2sbol/1
Created by: Amandeep Varia
Date created: 2016-10-17 11:00:00
Date modified: 2016-10-21 04:29:17
Superoxide Dismutase 3
| Types | DnaRegion |
| Roles | engineered_region Composite |
| Sequences | BBa_K1954005_sequence (Version 1) |
Description
Naturally, antioxidants break down harmful free radicals into less harmful substances like h202. It???s been found that in imbalance in the amount of free radicals and antioxidants leads to the damage of a cell therefore leading molecular ageing of a cell. An imbalance between generation of free radicals and antioxidant defences leads to oxidative stress in which cell antioxidants are at an insufficient level to keep free radicals below a toxic threshold.Superoxidise dismutase (SOD) is an important antioxidant enzyme in nearly all living cells exposed to oxygen and is present inside and outside the cell membrane. SOD enzyme???s catalyses the reaction O-2 + O-2 + 2H+ → H2O2 + O2.
There are three types of SOD enzymes:
SOD1 (Soluble - CuZnSOD) ??? Involved in removing oxidative stress causing ischemia-reperfusion injury and ischemic heart disease.
SOD2 (Mitochondrial - MnSOD) - SOD2 clears mitochondrial reactive oxygen species (ROS).
SOD3 (Extracellular - ECSOD) - protect the brain, lungs, and other tissues from oxidative stress.
SOD3 is found in the extracellular matrix of tissues and is ideally situated to prevent cell and tissue damage initiated by extracellularly produced free radicals. It is also the primary extracellular antioxidant enzyme found in the lungs and protects the extracellular matrix during lung injury. It???s been found that mutations in the SOD3 protein is associated with reduced lung function in adults and lung function decline in chronic obstructive pulmonary disease (COPD). Because of their anatomy, location and function, the lungs are highly susceptible to oxidative damage. One study also showed that SOD3 levels decreased as the mice aged in the lungs. Free radicals accumulate as we age, therefore the overexpression of SOD is one potential way to decrease the levels free radicals that accumulate.
Biosynthage have built a gene therapy device that reduces the amount of free radicals exposed to the lung cells, to reduce the ageing of the cells that lead to COPD and other age related diseases in the lungs. Our idea is to overexpress antioxidant enzyme SOD3 in the lungs through a gene therapy approach targeted towards people who are 30-40 years old. Our system is composed of a lentivirus backbone with the SOD3 gene. SOD3 will always be expressed in the epithelial cells, and will always be available to break down harmful free radicals into less harmful chemicals.
Our biobrick will also have SOD3 with GFP downstream, such that when we transfect our mammalian cells, we can see which cells have successfully taken our lentivirus system up.