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Revision as of 12:30, 3 June 2025
ModulesGene Editing: Technology Basics
The aim
To support research ethics reviewers in learning about gene editing technologies for the review of projects and proposals that include the use of gene editing. The content focuses on key technology basics, in a succinct manner, and signposts further learning opportunities for those who require more in-depth knowledge.
Learning outcomes
At the end of this module, learners will be able to:
- Explain the basics of gene editing and the role of CRISPR-Cas9.
- Describe possible fields of human application.
- Describe possible fields of non-human application.
- Identify the main risks associated with human and non-human applications.
CRISPR-Cas9
Some Functions of Gene Editing
Gene editing is used in many different types of research, and for many different purposes. Work through the following presentation to hear about some of the different functions.
Some functions of gene editing
Gene editing is used for many different purposes. Here are some examples:
Gene editing in organoids - Organoids are three-dimensional structures derived from stem cells that mimic the structure and function of human organs. Genome editing techniques can be applied to manipulate the genetic makeup of organoids, allowing researchers to study the effects of specific genetic mutations or modifications on organ development, function, and disease. For instance, genome editing can be used to introduce disease-relevant mutations into organoids, allowing researchers to assess drug efficacy, toxicity, and safety without the involvement of humans or animals.
Gene editing and embryoids - Embryoids, also known as ‘synthetic embryos’, are three-dimensional structures derived from stem cells that mimic the early stages of embryonic development. They serve as models for studying embryogenesis, organogenesis, and developmental disorders. Gene editing techniques can be applied to embryoids to manipulate their genetic makeup, enabling researchers to investigate the role of specific genes in embryonic development and disease. For instance, via gene editing, researchers can introduce disease-associated mutations into embryoids, allowing them to study disease mechanisms, screen potential therapies, and develop personalised treatment approaches.
Gene editing and xenotransplantation - Xenotransplantation involves the transplantation of living cells, tissues, or organs from one species to another. It holds potential as a solution to the shortage of human organs for transplantation. Gene editing technologies offer opportunities to overcome some of the barriers and challenges associated with xenotransplantation. For instance, gene editing can be used to modify the genomes of donor animals to make their organs more compatible with the recipient's immune system or to inactivate retroviruses genes thereby reducing the risk of viral transmission between species.
Gene Editing and Stem Cell Research
Stem cells are undifferentiated cells that have the ability to develop into various types of cells in the body. This unique characteristic makes them incredibly valuable for research.
The type of cells into which stem cells can differentiate depends upon whether they are omnipotent or pluripotent. Do you know what this means?
Gene Editing and Stem Cell Research cont.
Gene editing and stem cell research intersect in many different ways. For instance, stem cells, particularly induced pluripotent stem cells, can be derived from patients with genetic diseases. These cells can then be edited using CRISPR-Cas9 to introduce or correct disease-causing mutations, allowing researchers to study the underlying mechanisms of the disease in a controlled laboratory environment. This approach can also be used to screen potential drugs for treating genetic disorders.
Gene Therapy
When gene editing is used for therapeutic purposes, it is known as gene therapy. Watch the following two videos to find out more about what gene therapy is, and some of the primary benefits.
Gene therapy involves the introduction of genetic material or gene editing tools into cells to correct or compensate for a genetic defect, treat or prevent disease, or enhance cellular functions. Gene therapy falls into three main types:
- Gene transfer therapy, which involves introducing new healthy genetic material into cells to replace or supplement defective genes.
- Gene silencing, whereby small RNA molecules are used to silence or moderate the expression of specific genes.
- Gene editing, which involves the introduction of gene-editing tools that can change the existing DNA in the cell. CRISPR-Cas9 technologies can be used to add, remove or alter genetic material at precise locations in the genome, correcting mutations or disrupting harmful sequences.
Difference between Somatic and Germline Gene Editing
For each of the following characteristics, decide whether it relates to somatic gene editing or germline gene editing.
The key distinction between somatic gene editing and germline gene editing lies in the target cells and the heritability of the genetic modifications. Somatic gene editing involves making changes to the DNA of somatic cells, which are the non-reproductive cells of an organism.
Germline gene editing involves making changes to the DNA of germline cells, which are the cells that give rise to eggs and sperm.
Non-Human Applications of Gene Editing
In addition to the uses in human biomedical research, gene editing is also increasingly used in agricultural and environmental research, including the application of gene drive technologies.
Gene drive is a genetic engineering technique that aims to spread a specific genetic element in a population of non-human organisms resulting in a genetically modified organism (GMO). Unlike traditional Mendelian inheritance, where a gene can be thought of as having a 50% chance of being passed on to offspring, gene drive systems bias inheritance in favour of a particular gene variant, allowing it to spread rapidly within a population. CRISPR-Cas9 is often used to create gene drive systems because the technique allows for the introduction of gene drive elements.
CRISPR-Cas9 In Agriculture
CRISPR-Cas9 technology also has many implications for agriculture including the precise modification of plant genomes for crop improvement. Here are some examples:
CRISPR can be used to enhance the nutritional value of crops, for instance, via micronutrient biofortification of staple crops, to increase nutritional value. Biofortification is relatively new approach to dealing with deficiencies of micronutrients, especially in in low and middle-income countries. See, for example, the Golden Rice Project in the Philippines where a gene has been genetically modified to contain beta carotene, a plant pigment that the body converts into vitamin A.
Extended Shelf Life
CRISPR technology can be used to prolong the shelf life of fruits and vegetables by modifying genes involved in ripening and decay processes, thereby helping to reduce food waste.
Disease Resistance
By targeting specific genes responsible for susceptibility to certain diseases, CRISPR can be used to develop plants that are more resilient to pathogens, potentially reducing the need for pesticides.
Environmental Adaptation
What are the Risks Associated with Gene Editing?
Gene editing technologies hold great promise for treating genetic diseases, improving agricultural yields, and addressing many other challenges. However, they also come with ethical, social, and safety considerations. Some of the risks associated with gene editing include:
Off-Target Effects
Gene editing tools may unintentionally modify genomic regions other than the target, leading to unintended consequences. Off-target effects could potentially cause new genetic mutations or disrupt the function of other essential genes.
On-Target Effects
Gene editing tools may unintentionally modify the target DNA in the wrong way with unwanted deletions or insertions. For instance, the DNA coding for the Cas protein may become built into the DNA target sequence of the cell, which would lead to the gene in question not functioning properly.
Mosaicism
Genetic mosaicism is the presence of more than one genotype in one individual. Some cells in the target region undergo the desired genetic modification while others still carry the original DNA resulting in a mosaic pattern of edited and unedited cells. This can lead to problems in communication between cells.
Immunogenicity
The use of gene editing tools, especially those involving viral vectors to deliver editing components, may trigger an immune response in the organism. The immune response could limit the effectiveness of the treatment or cause adverse reactions.
Germline Gene Editing
The ability to edit the human germline, which includes sperm and egg cells, raises ethical concerns about the potential for heritable genetic modifications. The long-term consequences and unintended effects on future generations are not fully understood; if the modifications turn out to be harmful, they will not only have consequences for a single individual, but also for future generations.
Unintended Consequences
Modifying one gene may have unintended consequences for other genes or biological processes. For instance, the unintended consequences of releasing GMOs into the environment, could result in gene flow to wild populations, disruption of ecosystems, and the emergence of resistant pests or weeds. Or the de-extinction of certain species could lead to other species becoming extinct or other disruptions of the ecosystem.
Human Enhancement
End of Module Exam
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Thank you!Bibliography
UK Genetic Technology (Precision Breeding) Act 2023: https://www.legislation.gov.uk/ukpga/2023/6/contents/enacted
Association for Responsible Research and Innovation in Genome Editing (ARRIGE): https://www.arrige.org/
European Parliament, Directorate-General for Parliamentary Research Services, A Nordberg, et L Antunes. Genome editing in humans – A survey of law, regulation and governance principles. European Parliament, 2022. https://doi.org/10.2861/07058.
The Nuffield Council on Bioethics ethical review on genome editing: this document gives a good overview of the technique of gene editing as well as the ethical and legal questions surrounding it. From the examples given, there could be case studies being developed https://www.nuffieldbioethics.org/assets/pdfs/Genome-editing-an-ethical- review.pdf
The Nuffield Council on Bioethics social and ethical review on genome editing and human reproduction: very helpful background information on the topic of gene editing which can be used for designing case studies or other kinds of training modules https://www.nuffieldbioethics.org/assets/pdfs/Genome- editing-and-human-reproduction-report.pdf
A case study from The Royal Society about gene editing in human embryos: https://royalsociety.org/-/media/policy/projects/gene-tech/case-studies- keywords/case-study-genome-edited-human-embryos.pdf
A case study from The Royal Society about non-heritable human genome editing: https://royalsociety.org/-/media/policy/projects/gene-tech/case-studies- keywords/case-study-non-heritable-genome-editing.pdf
An overview of success stories related to gene editing and can be used for real life examples for what gene editing can and can’t do: https://media.nature.com/original/magazine-assets/d41586-021-02737- 7/d41586-021-02737-7.pdf
This article reflects on the fundamental ethical dilemma of using gene drives in mosquitoes and its possible effects on people in Africa: https://www.sciencenews.org/article/gene-drives-mosquito-malaria-crispr- africa-public-outreach
