What is a genome ?
- The genome of an organism is the whole of its hereditary information encoded in its DNA.
- Within DNA there is a unique chemical code that guides our growth, development and health.
- This code is determined by the order of the four nucleotide bases (DNA bases) that make up DNA, Adenine,Cytosine, Guanine and Thymine, A, C, G and T for short.
- DNA has a twisted structure in the shape of a double helix. Single strands of DNA are coiled up into structures called chromosomes.
- Our chromosomes are located in the nucleus within each cell. Within our chromosomes, sections of DNA are “read” together to form genes.
- Genome editing is an approach in which the genome sequence is directly changed by adding, replacing, or removing DNA bases. However, the genome is relatively resistant to change.
- If DNA could be easily altered, many essential cell functions would be disrupted in undesirable ways. To deter any changes from being inadvertently made to DNA, cells have inherent mechanisms to proofread and repair their genetic code.
- Remarkably, researchers have been able to take advantage of the cell’s DNA repair mechanisms to achieve genome editing.
- To accomplish this, scientists can use artificially engineered enzymes called nucleases to crack open DNA strands.
- In effect, these nucleases act as molecular scissors that form a break in the DNA double-stranded helix.
- Once a break is introduced in the DNA, the cell will detect a problem in its genetic code and quickly activate its repair machinery.
Methods of genome editing
- There are two major methods by which a cell can repair a break in its DNA:
- First, the cell can employ various enzymes to directly join the two ends of the DNA break back together. However, this process is very error-prone and often results in mutations.
- Second, a DNA sequence can be designed to be inserted along with a nuclease, such that when a cut is made in the DNA, the cell’s own repair mechanisms can use the DNA sequence supplied to replace an existing DNA sequence as it repairs the break. This method allows scientists to directly change genetic information in cells by introducing a correct version of a DNA sequence to replace an unwanted mutation.
- Genome editing is already being used by scientists as one of their many tools to develop cell and animal models for studying different diseases.
- Zinc finger nucleases (ZFNs), a type of nucleases has been tested as a therapeutic approach in many genetic diseases. For example, in treating Hemophilia, Huntingtons Disease etc.
Gene editing in embryos
- Chinese researchers made the first attempt at editing genes in human embryos in a laboratory experiment that didn’t work well. But it did raise the prospect of one day altering human heredity passing modified DNA to future generations.
- Preliminary research suggests that genome editing may be a promising therapeutic approach, but more work is needed prior to clinical testing in humans.
- Scientists are engineering animals with human like disorders to unravel the gene defects that fuel them.
- They’re building stronger immune cells, and developing potential treatments for muscular dystrophy, sickle cell disease and cancer.
- They’re trying to grow transplantable human organs inside pigs.
- They’re even hatching mutant mosquitoes designed to be incapable of spreading malaria, and exploring ways to wipe out invasive species.
- As for that preliminary embryo research, it’s nowhere near ready for real-world use, but there’s controversy over whether and how to continue such experiments to see if it eventually will work.
- At issue are tools to edit precisely genes inside living cells, finding specific sections of DNA to slice and repair or replace much like a biological version of cut-and-paste software.
- There are a few methods but one called CRISPR-Cas9 is so fast, cheap and simple for biologists to use that research is booming.
- Jennifer Doudna of the University of California co-invented this tool. Recently she gave a call for scientists, policymakers and the public to determine the right balance in how it’s eventually used which led to a gathering in December
- On one side are scientists who say the ultimate goal is to prevent parents from passing devastating diseases to their children. This technology is poised to transform preventive medicine
- British researchers, for example, plan to alter embryos to study early human development, work that could shed light on miscarriages. They argue that standard in-vitro fertilization techniques to test the genetics of embryos before they’re implanted, or before adoption, are alternatives. And they raise the spectre of parents who can afford designer babies with specific traits.
- A complete ban on such research could block important discoveries
- On the other side are critics who say that so-called germline editing altering sperm, eggs or embryos to affect future generations has been widely regarded as a line science shouldn’t cross.
- The medical arguments are tenuous and the possible social consequences are grave
- In the U.S., the National Institutes of Health won’t fund human germline editing research, although private funding is still possible. Laws and guidelines in other countries vary widely.
In December 2015, scientists of major world academies called for a moratorium on inheritable human genome edits, including those related to CRISPR-Cas9 technologies
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