Gene Therapy may be defined as a technique in which a patient (sufferer) is given healthy genes to replace the defective ones inherited from the parents, or to enhance the action/reaction of the genes they already have.
Must read: Gene Therapy- Definition, Types and Limitations
There are two basic types of human gene therapy:
(i) Somatic (body cell) gene therapy
In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into any cell other than a gamete, germ cell, gametocyte, or undifferentiated stem cell. Any such modifications affect the individual patient only, and are not inherited by offspring.
For further information on SOMATIC GENE THERAPY refer Gene Therapy- Definition, Types and Limitations
(ii) Germ line (sex cell) gene therapy
In this approach, cells of germinal epithelium or gametes or zygote are genetically modified to create an individual that will carry remedial gene(s) in the following generation.
Our reproductive cells, known as germline cells or germ cells, are those sex cells (eggs and sperm) that pass on genes from parents to their children. Germline gene editing involves altering the specific genes of an egg, sperm cell, or early embryo (i.e., up to five days after fertilization) in a laboratory dish. Germline gene editing removes, disrupts, alters, or corrects faulty elements of DNA within a gene in sex cells.
Why clinical use of germline gene editing is prohibited in many countries around the world?
The clinical use of germline gene editing is prohibited in many countries at present for good reasons, owing to significant scientific, ethical, and safety concerns associated with its use.
The potential benefit of clinical use of germline gene editing is that it might theoretically prevent a genetic disease in a yet-unborn person, but there are also substantial risks. Some risks are unknown, but others are well understood:
1 . It is neither safe nor effective at this time to use gene editing technologies on germline cells to attempt to prevent disease in a yet-unborn person, and that there are currently too many unknowns about this process for clinical use to proceed.
2 . Because genetic diseases are inherited, clinical use of germline gene editing would have potential multigenerational effects when the treated embryo develops, is born, and passes on the edited genes to children of their own. The potential benefits and potential harms for both the edited individual and the larger population may not be fully known or appreciated within the lifetime of the treated patient, and many generations would need to be studied to understand the long-term effects.
3 . The goal of gene editing is to make a targeted genetic change inside cells. Off-target effects are unwanted changes to the genome that occur in addition to the intended genetic change. All gene-editing techniques can create off-target mutations at locations in the genome other than the intended site. With clinical germline gene editing of very early embryos, off-target effects have the dangerous potential to exert their impacts on multiple organs and body systems.
4 . Mosaicism is a risk associated with clinical germline editing, in which multiple populations of cells that have different genetic makeups exist within a single edited person’s body. Mosaicism might occur if genetic editing happened after division of the initial single cell embryo into two cells. For example, if at the two-cell stage one of the cells acquires one type of edit while the other cell either has a different edit or no edit, mosaicism may result. Mosaicism is problematic because the genetic disease to be prevented may still occur if all the cells in the embryo do not have the desired edit.
Why is there an interest in Germline Gene Editing?
It’s important to know why some might be interested in using the technique in the years ahead. Somatic gene therapies are often used to treat patients who have genetic diseases. Somatic therapies involve transfer of genetic material to some targeted portion of our existing cells – and since one estimate says the average person has 37.2 trillion cells total, even a fraction of that is a lot of cells!
Parents who have or carry a faulty gene may be interested in germline editing technology. Early embryos only have a few cells, so the number of targeted cells for editing would be much smaller. As the embryo develops, those few edited cells would divide, and divide again, and could theoretically result in the birth of a child with many cells having the desired edit.
External link: https://en.wikipedia.org/wiki/Gene_therapy
PRACTICE QUESTIONS
QUES . Consider the following statements: UPSC 2020
1 . Genetic changes can be introduced in the cells that produce eggs or sperms of a prospective parent.
2 . A person’s genome can be edited before birth at the early embryonic stage.
3 . Human induced pluripotent stem cells can be injected into the embryo of a pig.
Which of the statements given above is/are correct?
(a) 1 only
(b) 2 and 3 only
(c) 2 only
(d) 1, 2 and 3
Ans (d) Germline gene therapy is when DNA is transferred into the cells that produce reproductive cells, eggs or sperm, in the body. Hence statement 1 is correct. A person’s genome can be edited before birth at the early embryonic stage. Hence statement 2 is correct. Human-animal chimeras are animals bearing human cells and organs. Researchers have experimented by injecting several different forms of human stem cells into pig embryos to see which cell-type would survive best. The cells that survived longest and showed the most potential to continue to develop were intermediate human pluripotent stem cells. Hence statement 3 is correct.
