1.2 Therapeutic Enzymes to Treat Thrombosis
A thrombus, also called a blood clot, is the final product of the blood coagulation step in hemostasis. It consists of insoluble fibrin, deposited platelets, accumulated white blood cells and trapped red blood cells. Thrombosis usually appears in the elderly, easy to cause diseases such as hypertension and arteriosclerosis.
Urokinase isolated from healthy human urine or kidney tissue culture can catalyze the lysis of plasminogen to plasmin, which exerting thrombolytic function by degrading fibrin clots, fibrinogen as well as coagulation factor V and Ⅷ in the blood circulation. Besides the plasmin can also increase ADP activity in the vessels and inhibit ADP-induced platelet aggregation, and prevent thrombosis.
Streptokinase extracted from streptococcus can activate plasminogen to dissolve blood clots to treat thrombosis. Nattokinase in natto is a fibrin protease that directly decomposes thrombus with a strong thrombolytic effect. At present, these three enzymes have been widely used in pharmaceutical production.
1.3 Therapeutic Enzymes to Treat Gastrointestinal Diseases
Used as a digestive agent clinically, therapeutic enzymes can supplement the deficiency of endogenous digestive enzymes to treat digestive disorders or promote digestion. Digestive enzyme preparations are essential in ensuring the digestion and absorption of the elderly. The pharmaceutical application of protease is initially in digestive medicines to treat indigestion and loss of appetite. Among them, chymotrypsin and trypsin are important enzymes for digesting food, usually being made into compound preparations with amylase and lipase to strengthen the efficacy.
1.4 Therapeutic Enzymes to Resist Tumors
L-aspartase is the first enzyme used to treat leukemia. Lacking asparagine synthetase in cancer cells, asparagine required for growth cannot be produced. As L-aspartase can cut off external supply of asparagine, it has a notable effect on cancer, especially leukemia treatment
1.5 Therapeutic Enzymes to Resist Virus
The replication process of hepatitis B virus (HBV) is similar to that of retrovirus. They firstly transcribe its DNA into pregenomic RNA (pgRNA) which will then be wrapped by DNA polymerase and core protein molecules as core particles where occurring the reverse transcription and positive-strand synthesis of DNA to complete the genome replication.
The c protein (HBsAg, HBcAg) expressed by HBvc gene is involved in the assembly of viral nucleocapsid, making it the target antigen of immune attack. Cutting genes in the c-region can inhibit the replication of HBv and block the expression of HBcAg. Some studies showed that the rate of inhibiting the expression of HBsAg and HBcAg in cells by ribozyme was 55% and 28% respectively. RzC, a kind of ribozyme, shows its potential in resisting HBV virus infection in HepG 2.2.15 cells, which may be a means of HBV gene therapy in the future.
Artificial kidneys, as one of the extracorporeal circulation devices, have developed rapidly in recent decades due to the development of medical enzymology. The artificial kidney is a device that uses the extracorporeal circulation to clean the blood by removing the metabolic waste from the patient's blood through the dialyzer before sending back to the body, which used to be expensive and inconvenient as a large volume of dialysate is required during the process. In 1968, T.M.S.Chang improved the artificial kidney by solving the problem with a glass column containing urease microcapsules at one end and activated carbon or ion exchanger at the other end. Later, the improvement of the compound enzyme ammonia removal system further enhanced the urea removal function of the artificial kidney.
In recent years, with the rapid development of researches on genetic engineering enzymes, chemical modification enzymes and protein engineering, it is expected to enhance the stability and prolong the life of traditional therapeutic enzymes, and reduce the antigenicity of exogenous enzymes.
New enzymatic therapies and methods such as enzyme-controlled drugs and target enzyme therapy will be further explored to enhance the specificity and reduce the side effects of drug therapy at the same time. Time will witness the more prominent development and industrialization of enzymes for diagnostics and drug treatment.