Gene Editing and Ethics Quiz

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Questions and Answers

What is the primary outcome of germinal genetic modification?

  • Temporary changes in somatic cells
  • No changes to the genome
  • Permanent changes in reproductive cells (correct)
  • Reversible modifications that can be cured

What major ethical concern was raised in the Jiankui case regarding the gene editing of embryos?

  • The research was conducted with full parental consent
  • It involved enhancing a genetic trait rather than treating a disease (correct)
  • The process was thoroughly peer-reviewed
  • The experiment had a clear therapeutic benefit

Which DNA repair mechanism is associated with random insertions or deletions that can lead to mutations?

  • Nonhomologous end-joining (correct)
  • Nucleotide excision repair
  • Homology-directed repair
  • Base excision repair

What was the significance of the 2018 event involving the twins Lulu and Nana?

<p>They were the first humans born after germline modification (D)</p> Signup and view all the answers

What main risk is associated with gene editing that results in mosaicism?

<p>Presence of varied alleles within the edited embryos (C)</p> Signup and view all the answers

Which gene was targeted in the Jiankui case for modification related to HIV protection?

<p>CCR5 gene (D)</p> Signup and view all the answers

What is the main criticism regarding the benefit-risk balance of Jiankui's experiment?

<p>The risks outweighed the potential benefits (C)</p> Signup and view all the answers

Which of the following statements about homology-directed repair (HDR) is accurate?

<p>It is more efficient than nonhomologous end-joining (D)</p> Signup and view all the answers

What type of enzyme is an endonuclease?

<p>An enzyme that cuts DNA (C)</p> Signup and view all the answers

What does CRISPR stand for?

<p>Clustered Regularly Interspersed Short Palindromic Repeats (A)</p> Signup and view all the answers

Which gene editing tool is characterized as being more difficult and expensive than CRISPR?

<p>TALENs (A)</p> Signup and view all the answers

Who were the key figures in elucidating the mechanism of CRISPR/Cas9 in 2012?

<p>Jennifer Doudna and Emmanuelle Charpentier (B)</p> Signup and view all the answers

What are the three phases of the natural CRISPR system?

<p>Acquisition, expression, and interference (C)</p> Signup and view all the answers

What is the purpose of the trial evaluating EDIT-101?

<p>To assess safety, tolerability, and efficacy for an inherited form of blindness. (D)</p> Signup and view all the answers

What gene is associated with Leber congenital amaurosis 10 (LCA10)?

<p>CEP290 (B)</p> Signup and view all the answers

Which experimental treatment showed promise for an inherited form of deafness?

<p>Gene therapy related to otoferlin. (D)</p> Signup and view all the answers

What is the significance of the case of Aissam Dam?

<p>He exemplifies successful gene therapy for hearing loss. (D)</p> Signup and view all the answers

What biotechnological concern was raised regarding CRISPR technology?

<p>Its potential impact will begin with agricultural applications rather than medical ones. (C)</p> Signup and view all the answers

What was the outcome of the PRRS virus inoculation in genetically modified piglets?

<p>Modified piglets remained healthy while regular pigs fell ill. (D)</p> Signup and view all the answers

What was the primary goal of the clinical trials mentioned in the context of gene therapy for deafness?

<p>To evaluate efficiency in restoring hearing. (C)</p> Signup and view all the answers

Which statement about the first experimental programs in gene therapies is true?

<p>The United States, Europe, and China are all involved. (A)</p> Signup and view all the answers

Which crop is made resistant to powdery mildew disease through gene editing?

<p>Triticum aestivum (A)</p> Signup and view all the answers

Which gene is targeted to confer resistance to bacterial blight in rice?

<p>OsSWEET11 and OsSWEET14 (B)</p> Signup and view all the answers

What type of changes does gene editing primarily introduce into crops?

<p>Small alterations in existing genes (C)</p> Signup and view all the answers

In the context of regulations, gene-edited crops in the European Union are treated the same as which of the following?

<p>Conventional genetically modified organisms (B)</p> Signup and view all the answers

Which disease is eliminated in Cucumis sativus L through targeted gene editing?

<p>Ring spot and vein yellowing (D)</p> Signup and view all the answers

What distinguishes gene editing from traditional GMOs?

<p>Gene editing enhances protein levels already present in organisms. (C)</p> Signup and view all the answers

Which disease is associated with Arabidopsis thaliana?

<p>Turnip mosaic virus (D)</p> Signup and view all the answers

Which of the following crops is treated to develop resistance against the leaf thickening disease?

<p>Nicotiana benthamiana (D)</p> Signup and view all the answers

What will occur if one parent carries two disease-causing alleles?

<p>All children will inherit the disease-causing genotype. (B)</p> Signup and view all the answers

What is true about expectant mothers who carry two disease-causing alleles?

<p>All offspring would inherit the disease-causing genotype. (B)</p> Signup and view all the answers

What is a characteristic of X-linked recessive diseases?

<p>All male offspring will inherit the disease despite their mother's genotype. (A)</p> Signup and view all the answers

Which statement reflects the ethical concerns of somatic gene editing (GE)?

<p>Somatic GE involves contentious ethical issues. (A)</p> Signup and view all the answers

What is a possible outcome if both parents carry two disease-causing alleles?

<p>At least some children will inherit the disease. (A)</p> Signup and view all the answers

Why might research efforts be directed away from certain genetic disease studies?

<p>Due to potential for controversial ethical implications. (C)</p> Signup and view all the answers

What determines whether male offspring are affected by X-linked recessive diseases?

<p>The mother's ability to pass the disease allele. (B)</p> Signup and view all the answers

What does the summit recommend regarding germline gene editing at the current time?

<p>A rigorous pathway should be defined before proceeding. (A)</p> Signup and view all the answers

What is the general stance of the scientific community on somatic gene editing?

<p>It is a promising approach to treating genetic diseases. (D)</p> Signup and view all the answers

What kind of therapy did Layla Richards receive for her leukemia?

<p>UCART19 cells via CAR-T cell therapy (A)</p> Signup and view all the answers

What was a notable outcome of the treatment received by Layla Richards?

<p>The cancer cells completely disappeared. (A)</p> Signup and view all the answers

Which of the following statements about the current state of somatic genetic modification is true?

<p>Clinical trials in this field are few but have started. (B)</p> Signup and view all the answers

What is the primary function of the CAR-T cell therapy in treating cancer?

<p>It modifies T lymphocytes to attack tumor cells. (A)</p> Signup and view all the answers

What was the initial condition of Layla Richards at 14 weeks of age?

<p>She was diagnosed with aggressive leukemia. (B)</p> Signup and view all the answers

How does the summit describe the current understanding of the scientific and technical requirements for germline gene editing?

<p>Too uncertain to permit clinical trials at this time. (A)</p> Signup and view all the answers

What is a key characteristic of UCART19 cells as described in the content?

<p>They are an experimental treatment based on TALENs. (C)</p> Signup and view all the answers

Flashcards

What is gene editing?

Gene editing is a powerful technology that allows scientists to precisely modify the DNA sequence of an organism. These alterations can range from correcting disease-causing mutations to introducing beneficial traits. Gene editing tools, like CRISPR-Cas, are revolutionizing various fields, including medicine, agriculture, and biotechnology.

What is Recombinant DNA technology?

Recombinant DNA technology involves combining DNA from different sources to create new genetic combinations. This is achieved by cutting and pasting DNA fragments using restriction enzymes and ligases, allowing the creation of novel molecules with potential applications in medicine and agriculture.

What is CRISPR-Cas?

CRISPR-Cas is a gene editing tool derived from a natural defense system found in bacteria and archaea. It consists of a protein (Cas) enzyme and a guide RNA (gRNA) that can target and cut specific DNA sequences. This targeted cutting allows for the insertion, deletion, or modification of genes, enabling precise genome editing.

What are ZFNs and TALENs?

Zinc Finger Nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs) are earlier gene editing technologies involving proteins that bind to specific DNA sequences and induce double-strand breaks. However, their high costs, complexity, and limitations have made them less popular compared to CRISPR-Cas.

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Who are the key figures in CRISPR-Cas?

Francisco Mojica, Emmanuelle Charpentier, and Jennifer Doudna are pioneers in the field of CRISPR-Cas gene editing. Mojica initially described repeated DNA sequences in archaea in 1993, while Charpentier and Doudna elucidated the mechanism of CRISPR-Cas9 and its potential for gene editing. Feng Zhang made advancements by using CRISPR-Cas9 on mammalian cells.

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Autosomal dominant disease

A genetic disorder where only one copy of the disease-causing allele is needed for an individual to be affected. The disease can be passed down from one parent to their child.

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Autosomal recessive disease

A genetic disorder where two copies of the disease-causing allele are needed for an individual to be affected. Both parents must carry the allele for the child to inherit the disorder.

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X-linked recessive disease

A genetic disorder where the gene responsible is located on the X chromosome. Males are more likely to be affected, as they have only one X chromosome.

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Somatic Gene Editing (SGE)

Gene editing that alters the genetic makeup of somatic cells (non-reproductive cells). The changes are not passed down to future generations.

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Germline Gene Editing (GGE)

Gene editing that alters genetic material in reproductive cells (sperm, egg, or early embryo). The changes can be passed down to future generations.

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Gene editing for treating genetic diseases

A promising approach to treat or cure genetic diseases by targeting the genetic causes directly.

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Current position on SGE

The scientific community is actively exploring the potential of SGE to treat genetic disorders, considering its ethical implications.

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Ethical considerations in SGE

The scientific community acknowledges the promise of SGE but emphasizes ethical considerations and further research. This approach focuses on addressing the genetic cause of diseases while minimizing potential ethical concerns.

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Nonhomologous End-Joining (NHEJ)

A DNA repair mechanism that joins two broken ends of a DNA molecule together without using a homologous template. It is an error-prone process that can lead to insertions, deletions, or rearrangements in the DNA sequence.

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Homology-Directed Repair (HDR)

A DNA repair mechanism that uses a homologous template to repair a damaged DNA molecule. It is considered a high-fidelity repair pathway.

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Germline Genetic Modification

Genetic modifications made in sperm or eggs, which are passed down to the next generation.

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NHEJ in DNA Repair

A type of DNA repair that occurs when a double-stranded DNA break is repaired without a homologous template. It is prone to errors and can lead to insertions, deletions, or rearrangements in the genome.

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Mosaicism

The occurrence of different genetic sequences within different cells of an organism. It can arise from errors during DNA replication or repair.

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Off-target Effects

The potential for unintended changes (mutations) to occur in the genome at locations different from the intended target site during gene editing.

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Genetic Enhancement

The process of creating a genetic change that enhances an organism's traits beyond what is naturally occurring. It is controversial due to ethical considerations.

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Human Germline Modification

The practice of manipulating the genetic makeup of human embryos before or during pregnancy, aiming to cure diseases or enhance traits.

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Somatic genetic modification

A type of gene editing where changes are made to the DNA of non-reproductive cells. These changes are not passed down to future generations.

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CAR-T cell therapy

Therapeutic approach involving extracting immune system cells, modifying them with gene editing to recognize and fight cancer, and then re-introducing them to the patient.

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TALENs

A type of gene editing tool that uses proteins to bind to specific DNA sequences and induce double-strand breaks. Less popular than CRISPR-Cas.

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Layla Richards

A young girl with a severe leukemia, treated with a revolutionary CAR-T cell therapy based on TALENs, showing its potential for curing cancer.

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Germline vs. somatic editing

Gene editing changes are not permanent, they are confined to the treated individual and do not affect their offspring.

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2018 International Summit on Human Genome Editing

A scientific community consensus on the potential of germline editing: While exciting, the technology is still too risky for clinical trials.

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Future of gene editing

The field of gene editing is showing promising progress, especially in areas like cancer treatment.

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Ethical considerations of gene editing

Gene editing, while powerful, needs careful consideration before widespread use.

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EDIT-101

An experimental medicine that is delivered via sub-retinal injection and is under development for the treatment of Leber congenital amaurosis 10 (LCA10), a rare, inherited form of blindness.

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Leber Congenital Amaurosis 10 (LCA10)

An inherited form of blindness caused by mutations in the CEP290 gene. It is a rare disorder that affects the retina.

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Otoferlin gene

A gene responsible for a protein essential for sound signal transmission from the ear to the brain.

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Gene therapy for deafness

A gene therapy approach is showing promise for treating an inherited form of deafness caused by mutations in the otoferlin gene.

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CRISPR technology

A powerful gene editing tool derived from a natural bacterial defense system used to precisely modify DNA sequences.

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CRISPR-edited livestock

The use of CRISPR technology to edit the genes of livestock, creating animals with desired traits and disease resistance.

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Porcine Reproductive and Respiratory Syndrome (PRRS)

A highly contagious viral disease affecting pigs, causing respiratory and reproductive problems.

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Sickle Cell Disease

A common condition affecting humans, characterized by red blood cells that are crescent-shaped, leading to pain and tissue damage.

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CRISPR-Cas9 in Crop Disease Resistance

CRISPR-Cas9 is a revolutionary gene editing technology used to modify crop genes, enhancing their resistance to diseases like powdery mildew in wheat and bacterial blight in rice.

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How does CRISPR-Cas9 work?

CRISPR-Cas9 works by precisely targeting and altering specific genes within an organism's DNA, allowing scientists to introduce or modify traits.

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TaMLO-A1 Gene in Wheat

The TaMLO-A1 gene in wheat is responsible for controlling powdery mildew resistance. By targeting this gene using CRISPR-Cas9, scientists can enhance the crop's defense against the fungus.

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OsSWEET11 and OsSWEET14 in Rice

OsSWEET11 and OsSWEET14 genes in rice are known to increase susceptibility to bacterial blight. CRISPR-Cas9 can be used to disable these genes, making the rice more resistant to the bacterial infection.

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CRISPR-Cas9 vs. GMOs

Gene editing techniques like CRISPR-Cas9 bring about precise changes in existing genes, unlike GMOs which introduce foreign genes, resulting in a safer approach to crop improvement.

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EU Regulation on CRISPR-Cas9 Crops

The European Union's ruling on CRISPR-Cas9 crops classifies them as GMOs, subject to stringent regulations.

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Applications of CRISPR-Cas9 in Crop Improvement

CRISPR-Cas9 can be used to introduce beneficial traits in crops, such as disease resistance, enhancing their productivity and reducing the need for pesticides.

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Random Mutagenesis vs. CRISPR-Cas9

Random mutagenesis introduces larger, less controlled changes in the genome compared to precise modifications achieved by CRISPR-Cas9, leading to a higher risk of unintended consequences.

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Study Notes

Unit 4: Gene Editing. CRISPR

  • Gene editing modifies the genome, contexts (epigenetic marks), or results (transcripts) using endonucleases, enzymes that cut DNA.

Previous Technology: Recombinant DNA

  • Recombinant DNA technology involves inserting a gene of interest into a plasmid, placing the plasmid into a bacterium, and growing the bacterium in a culture to create copies of the gene.
  • The resulting protein can be harvested and used in research and certain applications (e.g., pest resistance crops, treating diseases).

Genetic Editing

  • Recombinant DNA is a previous technology compared to gene editing.
  • Gene editing, using newer techniques like CRISPR, has greater precision and lower costs than recombinant DNA techniques.
  • Inaccuracies, ineffectiveness, and applicability factors are potential problems in gene editing.

Gene Editing Tools

  • ZFNs (Zinc Finger Nucleases): High cost, complex operation, and operating problems.
  • TALENs (Transcription Activator-Like Effector Nucleases): More challenging and expensive compared to CRISPR.
  • CRISPR-Cas: Easier and more affordable technology that has revolutionized this field.

CRISPR-Cas

  • A natural defense system in bacteria and archaea against viruses.
  • CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats): Repeating DNA sequences separated by short segments of foreign DNA, important component of the system.
  • Cas (CRISPR-associated): Proteins that form a complex with crRNA and work together to cut foreign DNA at specific locations.

The Natural System (CRISPR-Cas)

  • A 3-step process for defending against viruses in prokaryotic cells:
    • Acquisition: Foreign viral DNA is incorporated into CRISPR locus.
    • Expression: CRISPR RNA (crRNA) is processed from the CRISPR locus and forms a complex with Cas proteins.
    • Interference: The crRNA-Cas complex targets and degrades matching viral DNA, preventing infection.

CRISPR as a Gene Editing Tool

  • Timeline of significant milestones in CRISPR development, research, and application.
  • In 1987, CRISPR was first reported.
  • Between 2000 and 2014, discoveries about CRISPR-Cas systems and their applications in various fields emerged.
  • In 2012, Charpentier and Doudna revealed the mechanism of CRISPR/Cas9 and demonstrated its potential for gene editing.
  • The Nobel Prize in Chemistry 2020 was granted to Emmanuelle Charpentier and Jennifer A. Doudna for discovering this method.

DNA Repair Mechanisms

  • Non-homologous end joining (NHEJ): A fast repair mechanism, but prone to errors like insertions or deletions.
  • Homology-directed repair (HDR): A more precise repair pathway where a template is used to repair the DNA break.

###Applications of CRISPR

  • Gene therapy has promising potential
  • Applications in medicine, including drug development, animal models, gene surgery, diagnostics, and materials science, as well as biotechnology.
  • Uses in agriculture (e.g., crops resistant to diseases and environmental factors).
  • Germline genetic modification affects reproductive cells (sperm and egg) or early embryonic development and results in heritable changes to future generations.

Medical Applications

  • Somatic genetic modification targets non-reproductive cells (like stem cells) for treating diseases such as cancer and genetic disorders.
  • Germline modification targets reproductive cells and early embryos.

CRISPR Case Examples

  • Layla Richards received treatment for leukemia using CAR-T cell therapy which was based on a newer gene editing technology (TALENs).
  • A woman with sickle cell disease was cured using CRISPR gene editing to change a specific gene.

Risks and Ethical Considerations Associated with CRISPR

  • Off-target effects
  • Mosaicism
  • Risks associated with genome editing, including potential for unintended mutations and safety/ethical issues.
  • Ethical issues related to using CRISPR on human germline cells for modifications that will affect future generations of individuals.
  • Unfavorable benefit-risk balance, and falsified ethical documents.
  • Potential risks to the ecosystem, food chain, and appearance of new pests.
  • The possibility of the spread of mutated guide RNAs, and dual use technology of the method itself

CRISPR-Edited Plants

  • Specific examples of plant varieties or crops altered to be resistant to environmental stressors or diseases.

Crops Resistant to Diseases

  • Specific examples of crop varieties or rice that have been made resistant to disease using CRISPR/Cas9.
  • Some crops have been genetically modified to resist diseases (e.g., rice with enhanced disease resistance).

Transgenic Organisms vs. Gene Editing

  • Differentiate between using foreign genes (transgenic) vs. making small alterations in existing genes (gene editing).
  • How they apply to organisms.

EU Regulations

  • Restrictions on the use of CRISPR in plant gene editing.
  • Research in the EU regarding genome editing.

Safety and Additional Notes

  • Safety and ethical aspects of CRISPR.
  • Need for lengthy analysis of characteristics when testing and selecting gene-edited organisms.

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