Gene Editing Technology
Gene Editing Technology
CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeats, is a groundbreaking tool in genetic engineering that enables precise DNA edits. The term CRISPR originally referred to repeating DNA sequences discovered in the bacterial immune system. These repeats are separated by spacer sequences—remnants of viral DNA that help bacteria recognize and defend against future infections.
To target DNA for editing, CRISPR requires two key elements: a protospacer adjacent motif (PAM) and a Cas (CRISPR-associated) nuclease. The PAM sequence is essential for identifying where the cut will be made, while the Cas nuclease (most commonly Cas9) is the enzyme that cleaves the DNA. Cas9 also requires a guide RNA (gRNA), which directs the enzyme to the specific DNA site. The gRNA is made up of two components:
CRISPR RNA (crRNA): complementary to the target DNA sequence.
trans-activating crRNA (tracrRNA): a scaffold that binds to the nuclease.
Together, the gRNA and Cas9 create a double-stranded break at the target site. Once the DNA is cut, the cell attempts to repair it through one of two main pathways:
Non-homologous end joining (NHEJ): the cell rejoins the broken DNA ends, often introducing small insertions or deletions.
Homology-directed repair (HDR): the cell uses a DNA template (which can be supplied by scientists) to repair the break, allowing for precise substitutions or insertions.
Beyond simple editing, modified versions of CRISPR can also be used to activate or repress gene expression without changing the DNA sequence itself.
CRISPR can be applied in two main ways: somatic editing and germline editing.
Somatic gene editing alters cells in an individual’s body but does not affect reproductive cells. As a result, the changes are not heritable. This approach has been studied in research settings for monogenic disorders, which are conditions caused by mutations in a single gene such as cystic fibrosis.
Germline gene editing modifies all cells in an embryo, including reproductive cells, which means the changes can be passed on to future generations. Because of its far-reaching and unpredictable consequences, germline editing is much more controversial and tightly regulated.
A well-known case highlighting these concerns occurred in 2018, when Chinese researcher He Jiankui announced the birth of twin girls whose CCR5 genes had been edited to confer resistance to HIV. The experiment was widely condemned as unsafe and unethical. Jiankui was sentenced in 2019 to three years in prison and fined three million yuan for violating medical regulations.
Our research centers on autism spectrum disorder (ASD), which the CDC defines as a developmental disability influenced by both environmental and genetic factors. Autistic individuals may communicate, behave, and learn differently from non-autistic individuals, though experiences and support needs vary widely.
The DSM-5 identifies two core diagnostic features of autism:
Persistent deficits in social communication and interaction across multiple contexts.
Restricted, repetitive patterns of behavior, interests, or activities.
Autism itself is not always accompanied by intellectual disability, but the two co-occur in about 45% of cases.
Hundreds of genes have been associated with ASD, many of which are involved in brain development. However, not all have been confirmed, and carrying variations in these genes does not guarantee autism. Genetic factors are estimated to account for 40–80% of autism risk, alongside environmental factors such as parental age and birth complications. Only a few ASD-related conditions, like Rett syndrome and Fragile X syndrome, have monogenic causes. In animal studies, for example, scientists were able to reduce repetitive behaviors in mice with Fragile X syndrome by restoring the Fmr1 gene.
Because CRISPR currently edits only single genes, it is not well suited for polygenic conditions like autism, which are influenced by multiple genes and environmental factors. The potential of CRISPR as a treatment would likely vary from person to person and remains uncertain. Nevertheless, given that technology often advances faster than regulation, it is crucial to consider the ethical implications of such applications in advance.
Despite its promise, CRISPR faces several technical and safety challenges:
Off-target effects: unintended edits at non-target sites, which can disrupt healthy genes.
DNA damage response: double-strand breaks can trigger apoptosis (programmed cell death) rather than repair.
Immune response: Cas9 can sometimes provoke an immune reaction in human hosts.
Mosaicism: in embryos, edits may occur inconsistently, leaving some cells unedited.
Researchers are actively developing strategies to minimize these risks as CRISPR technology advances.
Autism spectrum disorder: MedlinePlus Genetics. (n.d.). Retrieved May 1, 2022, from https://medlineplus.gov/genetics/condition/autism-spectrum-disorder/
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CDC. (2022, March 31). Basics about autism spectrum disorder (ASD). Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/autism/facts.html
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