`star` Recombinant DNA technology for Therapeutic uses
`star` Genetically Engineered Insulin
`star` Gene Therapy


● The `color{violet}("recombinant DNA technological processes")` have made immense impact in the area of `color{violet}("healthcare by enabling mass production")` of safe and more `color{violet}("effective therapeutic drugs")`.

● Further, the `color{violet}("recombinant therapeutics")` do not induce `color{violet}("unwanted immunological")` responses as is common in case of similar products isolated from `color{violet}("non-human sources")`.

● At present, about `color{violet}("30 recombinant therapeutics")` have been approved for `color{violet}("human-use")` the world over.

● In `color{violet}("India, 12")` of these are presently being marketed


● Management of `color{violet}("adult-onset diabetes")` is possible by taking `color{violet}("insulin")` at `color{violet}("regular time")` intervals.

● `color{violet}("Insulin")` used for `color{violet}("diabetes")` was earlier extracted from `color{violet}("pancreas")` of `color{violet}("slaughtered cattle")` and `color{violet}("pigs")`.

● `color{violet}("Insulin")` from an `color{violet}("animal source")`, though caused some patients to develop allergy or other types of reactions to the `color{violet}("foreign protein")`.

● `color{violet}("Insulin")` consists of two `color{violet}("short polypeptide chains: chain A and chain B")`, that are linked together by `color{violet}("disulphide bridges")`.

● In `color{violet}("mammals, including humans, insulin")` is `color{violet}("synthesised")` as a `color{violet}("prohormone")` (like a pro-enzyme, the pro-hormone also needs to be processed before it becomes a fully mature and functional hormone) which contains an extra stretch called the `color{violet}("C peptide")`.

● This `color{violet}("C peptide")` is not present in the `color{violet}("mature insulin")` and is removed during `color{violet}("maturation")` into `color{violet}("insulin")`.

● The main challenge for `color{violet}("production of insulin")` using `color{violet}("rDNA")` techniques was getting `color{violet}("insulin assembled")` into a `color{violet}("mature form")`.

● In `color{violet}("1983, Eli Lilly")` an American company prepared two `color{violet}("DNA")` sequences corresponding to A and B, chains of `color{violet}("human insulin")` and introduced them in `color{violet}("plasmids of E. coli")` to produce`color{violet}(" insulin chains")`.

● `color{violet}("Chains A and B")` were produced separately, extracted and combined by `color{violet}("creating disulfide bonds")` to form `color{violet}("human insulin")`.


● `color{violet}("Gene therapy")` is a `color{violet}("collection of methods")` that allows correction of a `color{violet}("gene defect")` that has been `color{violet}("diagnosed")` in a `color{violet}("child/embryo")`.

● Here `color{violet}("genes")` are inserted into a `color{violet}("person’s cells and tissues")` to treat a `color{violet}("disease")`.

● Correction of a `color{violet}("genetic defect")` involves delivery of a `color{violet}("normal gene")` into the `color{violet}("individual or embryo")` to take over the function of and compensate for the `color{violet}("non-functional gene")`.

● The first `color{violet}("clinical gene therapy")` was given in `color{violet}(1990)` to a `color{violet}("4-year old girl")` with `color{violet}("adenosine deaminase (ADA) deficiency")`.

● This enzyme is crucial for the `color{violet}"immune system"` to function.

● The disorder is caused due to the `color{violet}("deletion of the gene")` for `color{violet}("adenosine deaminase.")`

● In some children `color{violet}("ADA deficiency")` can be cured by `color{violet}("bone marrow transplantation")`; in others it can be treated by `color{violet}("enzyme replacement therapy")`, in which `color{violet}("functional ADA")` is given to the patient by `color{violet}("injection")`.

● But the problem with both of these approaches that they are not `color{violet}("completely curative")`.

● As a first step towards `color{violet}("gene therapy, lymphocytes")` from the blood of the patient are `color{violet}("grown")` in a `color{violet}("culture outside")` the body.

● A `color{violet}("functional ADA cDNA")` (using a retroviral vector) is then introduced into these `color{violet}("lymphocytes")`, which are `color{violet}("subsequently returned")` to the patient.

● However, as these `color{violet}("cells")` are not `color{violet}("immortal")`, the patient requires `color{violet}("periodic infusion")` of such `color{violet}("genetically engineered lymphocytes")`.

● However, if the `color{violet}("gene isolate")` from `color{violet}("marrow cells producing ADA")` is introduced into `color{violet}("cells")` at early `color{violet}("embryonic stages")`, it could be a `color{violet}("permanent cure")`.