Directions: After students have had a chance to review the article “Gene therapy fixes rare skin disease,” lead a classroom discussion based on the questions that follow.
1. What are stem cells?
Stem cells can develop into many different cell types in the body. The new cells produced after stem cell division can either remain stem cells or can become another type of specialized cell. Stem cells can replenish other cells, serving as a sort of internal repair system. Pluripotent (sometimes called totipotent) stem cells, such as those found in early embryos, can give rise to any type of cell in the body, depending on the hormones, cell-cell signals and other stimuli that the stem cells are exposed to. Multipotent stem cells (sometimes called adult stem cells) can give rise to any type of cell within a limited range. For example, a hematopoietic stem cell could give rise to any of several different types of white blood cells, but not heart cells or liver cells.
2. How might stem cells be used for therapy?
Stem cells could be given the right stimuli to differentiate into specific cell types and regenerate damaged organs, limbs or other tissues. For example, if a person no longer has enough stem cells, induced pluripotent stem cells could be made from other adult cells, which could then help to replace damaged tissue. Cells from another person (or embryo) could theoretically be manipulated and used, but to avoid being attacked by the patient’s immune system, they would need to come from a genetically similar or identical donor, or need to be genetically modified to look more similar to the patient’s own cells.
3. What methods can be used to change the DNA in a cell for gene therapy?
A virus can be used to carry and insert new genes in DNA. Alternatively, if non-viral DNA is packaged properly, such as in a liposome bubble or on a nanoparticle, it can sometimes get incorporated into a cell’s DNA. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and other techniques can be used to remove or edit existing genes within a cell.
4. How can gene therapy be used to repair genetic abnormalities in cells?
It is easier to do gene therapy under laboratory conditions in smaller numbers of cells instead of in a patient. Germline gene therapy is used on germ cells — embryos, sperm and eggs, or the cells that give rise to them; genetic modifications in these types of cells may help the resulting person and would be passed down to their children. Currently, germline gene therapy techniques are not used in people. Fertilized eggs that are modified using such techniques for research purposes are either not viable to begin with, or are not allowed to develop into fetuses. Somatic cell gene therapy makes genetic changes to non-germline cells, and thus, would not be passed down to the patient’s children. Somatic cell therapy is more successful when cells can be temporarily removed from a patient, treated with gene therapy in a lab, and then reintroduced in the patient. Somatic cell therapy was described in “Gene therapy fixes rare skin disease.” Gene therapy of somatic cells while they remain inside a patient can be done, but it is harder to ensure that enough of the intended cells receive the therapy.
5. What are some potential risks of gene therapy?
A patient’s immune system might attack a viral gene therapy vector or the patient’s cells that have been infected by that viral vector. Non-therapeutic genes that remain in the viral vector and are necessary for its function might produce symptoms of infection or trigger unwanted cell division (cancer). New gene sequences that integrate in the wrong place might damage an important and previously healthy gene or trigger unwanted cell division (cancer). Gene therapy methods might accidentally target the wrong gene some of the time.
6. Students should assemble into groups based on which of the following statements best describes how the students feel. Once students gather into groups, allow students time to discuss their beliefs and do additional research. Have groups think about additional factors that could affect or change their position, like the cost and availability of gene therapy. Then have each group of students explain why they believe their statement and address counterarguments from other groups:
- Gene therapy should not be used on humans.
- Gene therapy should be used on humans to cure potentially fatal illnesses (“butterfly” skin, cystic fibrosis), but not for any other reason.
- Gene therapy should be used on humans to cure potentially fatal illnesses, but also other, generally non-fatal health risks (tendency toward nearsightedness, obesity, baldness).
- Gene therapy should be used on humans to cure both fatal and non-fatal health risks, but also to alter intellect, physical appearance or any other characteristic students (or their parents) might desire.
- Gene therapy should be used on humans for any purpose, even giving people hearing ranges beyond what people can normally hear, the ability to see colors not normally visible to humans or tolerance to extreme temperatures.
1. What are laminins? What is the extracellular matrix?
Laminins are large proteins that help to form the extracellular matrix, which is the scaffold between cells that cells can attach to so that a multicellular organism can keep its shape. Other important proteins in the extracellular matrix include collagens, elastins and fibronectins.
2. How do cells stick to the extracellular matrix?
Glycoproteins are proteins covered with sugars, and sugars can be very sticky. Glycoproteins, such as integrins protruding from the surfaces of cells, can stick to glycoproteins in the extracellular matrix (such as laminins and fibronectins). In some cases, some hook-shaped proteins, such as cadherins on cell surfaces, directly grab hold of each other.
3. Mutations in laminin genes can cause the “butterfly” skin condition, but what are possible effects of mutations in collagen genes?
Collagen proteins are the most abundant component of the extracellular matrix and help to make it full and stiff. Mutations in genes that produce collagen proteins can make tissues hyperelastic. One example is Ehlers-Danlos syndrome, in which patients have very stretchy skin, plus potential joint or cardiovascular symptoms.
ENGINEERING AND EXPERIMENTAL DESIGN
1. How could you use laminins for other applications?
Laminin proteins could be used to coat surfaces that cultured cells attach to when growing sheets of skin in the lab, make biological materials made of webs of proteins, pre-coat a medical implant so that tissues in the body would rapidly bind and potentially adapt to the implant or mass-produce extracellular matrix that could be surgically grafted onto wounds to help them heal more quickly.
2. “Gene therapy fixes rare skin disease” mentioned genetic-barcode-like analysis of cells. What other applications could there be for genetic barcoding methods?
Other genetic barcoding methods could include monitoring and responding to bacteria in the human body, different cancer cell lineages in a cancer patient, different lineages of a pathogen in an infected person (for mutation-prone pathogens such as HIV, tuberculosis or malaria), or keeping track of cloned animals in laboratory experiments or in agricultural use.
3. In addition to treating patients with the “butterfly” skin disease, what are some other possible applications of treating and growing skin?
Skin grafts could be used for burn patients and gene therapy could be used to treat skin cancer, susceptibility to and damage from sunburns and the effects of aging on skin, for instance. Gene therapy could also be used to alter the color or appearance of skin as well as make skin stronger and more resistant to damage.
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