3.7.6 Genetic modification

3.7.6 Genetic modification

Genetic Modification

Genetic modification refers to the process of altering the DNA of an organism using biotechnology techniques. This can be done for a variety of purposes, including improving the characteristics of plants and animals, producing pharmaceuticals, and studying the function of genes. There are several methods that can be used to genetically modify organisms, including traditional breeding techniques, gene targeting, and genome editing.

Genome editing is a type of genetic modification that involves making precise changes to specific parts of an organism’s genome. It is usually done using enzymes that can cut DNA at specific sequences, such as CRISPR/Cas9. Once the DNA is cut, it can be repaired by the cell’s own repair mechanisms, which can result in the insertion, deletion, or modification of specific DNA sequences. Genome editing has the potential to be more precise and efficient than other methods of genetic modification, but it also raises ethical concerns because it has the potential to be used to create genetically modified organisms with characteristics that could not occur naturally (Baltimore et al., 2015).

Genetic modification and genome editing techniques are relevant to psychiatry in several ways:

Psychiatric relevance:Summary:
Understanding the genetic basis of mental disordersGenetic factors are thought to play a role in many mental disorders, such as schizophrenia, depression, and bipolar disorder. Studying the genetics of these conditions can help researchers understand the biological basis of these disorders and develop new treatments.
Developing animal modelsScientists can use genetic modification techniques to create animal models of mental disorders by introducing specific genetic changes into the genomes of mice or other animals. These models can be used to study the development and progression of mental disorders and to test new treatments.
Developing new treatmentsGenome editing and other genetic modification techniques can be used to develop new treatments for mental disorders. For example, researchers are exploring the use of CRISPR/Cas9 to edit the genomes of cells in order to correct genetic defects that contribute to mental disorders.
Ethical considerationsThe use of genetic modification and genome editing techniques in psychiatry raises a number of ethical concerns, such as the potential risks and benefits of these technologies and the implications for human enhancement. These issues are being actively debated by scientists, ethicists, and the general public.

(McInerney, 2017)

Zinc Finger Nuclease:

Zinc finger nucleases (ZFNs) are enzymes that can be used for genome editing. They consist of a DNA binding domain, which is made up of zinc fingers that can bind to specific sequences in the genome, and a nuclease domain, which can cut DNA. ZFNs can be engineered to target almost any sequence in the genome, making them a highly flexible tool for genome editing.

Like CRISPR/Cas9 and TALENs, ZFNs work by creating a double-stranded break in the DNA at a specific location. This break is then repaired by the cell’s own repair mechanisms, which can result in the insertion, deletion, or modification of specific DNA sequences. ZFNs have been used to edit the genomes of a variety of organisms, including plants, animals, and human cells.

While ZFNs have been widely used for genome editing, they have been largely superseded by CRISPR/Cas9, which is generally easier to use and has a higher editing efficiency. However, ZFNs may still be used in some applications where CRISPR/Cas9 is not suitable (Kim, 1996).

Transcription Activator-Like Effector Nucleases:

Transcription activator-like effector nucleases (TALENs) are enzymes that can be used for genome editing. They consist of a DNA binding domain, which allows them to bind to specific sequences in the genome, and a nuclease domain, which can cut DNA. TALENs can be engineered to target almost any sequence in the genome, making them a highly flexible tool for genome editing.

Like CRISPR/Cas9, TALENs work by creating a double-stranded break in the DNA at a specific location. This break is then repaired by the cell’s own repair mechanisms, which can result in the insertion, deletion, or modification of specific DNA sequences. TALENs have been used to edit the genomes of a variety of organisms, including plants, animals, and human cells.

While TALENs have been widely used for genome editing, they have been largely superseded by CRISPR/Cas9, which is generally easier to use and has a higher editing efficiency. However, TALENs may still be used in some applications where CRISPR/Cas9 is not suitable (Christian, 2011).

CRISPR

A specific “target” location in the genome can be changed by scientists using genome editing. “CRISPR” is the name of one of the methods that have sparked the greatest interest because of its effectiveness and simplicity. CRISPR stands for “clustered regularly interspaced short palindromic repeats“. The technique that bacteria developed to defend themselves against viruses serves as the foundation for CRISPR technology. A technique for genome editing has now been created by scientists using parts of the CRISPR system. The CRISPR system consists of two parts: a “nuclease” (i.e., a DNA-cutting protein) called Cas9 and a “guide RNA” (gRNA) molecule with the same sequence as the target site in the genome.

CRISPR-associated (Cas) genes:

When choosing a platform for gene editing, four things should be taken into account: specificity, target site choice, effectiveness, and ease of design. CRISPR-Cas9 is typically the most effective and simple to employ since it targets the specified genomic sequence with a high degree of precision and predictability while requiring less labour. By introducing numerous sg RNAs, the technique also enables the simultaneous editing of different genes.

CRISPR-Cas9 gene editing works by directing the Cas9 protein to a specific target with the help of a guide RNA (gRNA). Cas9 cleaves the DNA after binding to the target, which is then repaired by the cell’s DNA-repair machinery. This repair method is deemed unpredictable and heterogeneous without a template, making it unsuitable for precise editing. Precision editing, on the other hand, is desperately needed for research of basic gene function as well as the correction of mutations linked with genetic diseases (Cong, 2013) (Jinek, 2012).

References:

(1) Baltimore, D., Berg, P., Botchan, M., Carroll, D., Charo, R.A., Church, G., Corn, J.E., Daley, G.Q., Doudna, J.A., Fenner, M., Greely, H.T., Jinek, M., Martin, G.S., Penhoet, E., Puck, J., Sternberg, S.H., Weissman, J.S. and Yamamoto, K.R. (2015). A prudent path forward for genomic engineering and germline gene modification. Science, [online] 348(6230), pp.36–38. doi:10.1126/science.aab1028.

(2) Christian, M., & Cermak, T. (2011). TALENs: A widely applicable technology for targeted genome editing. Nature Reviews Molecular Cell Biology, 12(4), 356-361.

(3) Cong, L., et al. (2013). Multiplex genome engineering using CRISPR/Cas systems. Science 339(6121), 819-823.

(4) Jinek, M., et al. (2012). A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096), 816-821.

(5) Kim, D. H., et al. (1996). Targeted mutagenesis of the HPRT gene using zinc-finger nucleases. Nature, 380(6573), 635-638.

(6) McInerney, J. J., & Callaway, E. (2017). Gene editing: A new era of psychiatric research. Nature Neuroscience, 20(11), 1449-1457.