Manipulating Gene Drive Spread of Fly Species Using CRISPR

Aayushi Gaur; U.I.E.T, Kurukshetra University

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, accompanying it ‘Cas’, an acronym for CRISPR-associated protein. Cas can be readily modified to target particular portions of DNA and to turn genes on/off without changing their sequence. It is a form of genome editing technology that is utilized to make double-stranded breaks in DNA at certain locations. CRISPR is unique as it is extremely precise, similar to a pair of microscissors used to cut DNA. We can go inside cells and edit DNA in a similar fashion to how a document is edited, allowing scientists to correct genes.

CRISPR-Cas is easier to use, cheaper, and more accessible than prior genome editing methods, as stated in diverse policy reports (Nuffield Council on Bioethics, 2016; NASEM, 2017; COGEM, 2018) and natural science papers. It is being rapidly used in various scientific sectors. CRISPR-Cas appears to eliminate technological hurdles in the development of genetically engineered humans, animals, and plants.

From disease elimination to healthier food sources, CRISPR-based technologies have immense potential to improve human health and safety. CRISPR-based gene drives are being created to prevent the spread of fatal diseases like malaria and dengue fever by spreading specified features through targeted populations.

Understanding what gene drive is

A gene drive is a technique that drives particular genes into the population of a species. Gene drives do this by dramatically boosting the likelihood of a certain gene being handed down to an organism’s progeny. It allows genes to spread quickly within a population and therefore bypasses natural selection. Just like party invites, gene drive disseminates a gene across an entire species’ population.

Functioning of gene drive

The technique of gene drive works by using directed repair gene editing. Through the use of a donor template, a new gene known as the driven gene can be inserted at a specific cut point. CRISPR proteins, like all proteins, have accompanying genes that guide cells on how to create them. In a gene drive, the donor template contains both, the gene to be transmitted and genes coding for CRISPR proteins. As a result, both the driven gene and CRISPR molecules’ genes are inserted at the cut spot. A gene drive is constantly modifying the genome because it carries instructions for making additional CRISPR proteins. It even modifies the genes handed down through the generations to contain the driven gene. As a consequence, after just a few generations, the driven gene will be found in an entire population of a species.

A gene drive with a built-in genetic barrier has been devised by scientists at the University of California, San Diego, to keep the drive under control. The researchers, led by molecular geneticist Omar Akbari, created synthetic fly species that, when released in large numbers operate as gene drives that may spread locally and be reversed if desired. The researchers describe their SPECIES (Synthetic Postzygotic Barriers Exploiting CRISPR-based Incompatibilities for Engineering Species) innovation as a proof-of-concept that can be used on other species such as insect disease vectors. Another plausible use of the spread of gene drives is that it can limit pests that prey on vital food crops. Gene drives are challenging to control because they have the ability to spread beyond their intended bounds. SPECIES is a population control strategy that is both safe and reversible.

Working with the fly species – Drosophila melanogaster, UC San Diego researchers collaborated with colleagues at the California Institute of Technology, UC Berkeley, and the Innovative Genomics Institute to create flies that encode SPECIES systems that are incompatible with wild Drosophila melanogaster.

“Even though speciation happens consistently in nature, creating a new artificial species is actually a pretty big bioengineering challenge” said Anna Buchman, the paper’s first author. The SPECIES approach is appealing because it streamlines the process by giving us a set of tools that any species may employ to gently bring about speciation.

Speciation –

Speciation refers to the division of a single species into two or more genetically different species. It is the complicated process of creating a new species from existing ones. Speciation, according to its definition, occurs as a result of ongoing gene mutation. After a series of habit modifications, living beings develop distinct features, some of which are passed down to their children.

The concept behind the creation of SPECIES is inspired by the natural process of new species generation (speciation). When individuals of a single species physically split over time, for example, due to a new land formation, earthquake separation, or another geological event, a new species might emerge. If the new species finally mates with the old species, biological alterations caused by the separation might result in unviable offspring due to reproductive isolation, a natural phenomenon.

SPECIES –

In theory, if SPECIES are deployed in sufficient numbers in the wild, they may controllably drive through a population, displacing all of their wild counterparts as they spread. SPECIES mosquitoes, for example, may be bred to inherit a genetic feature that prevents them from transmitting malaria.

As SPECIES and wild-type mosquitoes are incompatible, their numbers may be managed and reversed by keeping them below 50% of their threshold population. This enables containment and, if required, reversal of the disease’s spread. With the return of wild-type populations, the SPECIES barrier’s duty of temporarily replacing wild-type populations will be completed, and their numbers will be lowered. Essentially, this enables us to leverage the full potential of gene drives — such as disease eradication or crop protection — without the significant risk of uncontrollable spread.

Is CRISPR gene drive a matter of concern?

Many scientists and ethicists are concerned about gene drives spreading unrestrained. How can scientists prevent gene drives from spreading uncontrolled throughout populations once they’ve been released into the wild?

Before gene drives are widely used in organisms, certain problems must be addressed. Employment of gene drives poses a considerably greater risk to the ecosystem since they can wipe out an entire species, destroy a food supply for other species, or accelerate the spread of exotic pests. Targeting disease-carrying mosquitos in the wild may have unintended consequences for other species.

Scientists are concerned, for example, about possible unexpected (off-target) consequences of CRISPR/Cas9 technology, such as indirect effects on other genes in the organism, which might lead to death or incapacity to reproduce. Furthermore, the time it takes for the impacts of gene drives to diffuse across the population should be investigated further. Finally, changing one creature may have the potential to disturb the balance of other organisms that rely on the transformed species, such as predators. Before introducing gene drives into the environment, these issues must be well investigated and understood.

Researchers are actively working in this field to overcome all the plausible problems that gene drive possesses, and to rectify the same they have come up with SPECIES. SPECIES can be seen as a benchmark in the history of gene drive as its objective is to introduce gene drive in a manner that can be controlled and be reversed when needed.

Many questions still remain unsolved, including the following: Can CRISPR’s off-target cut lead to unintended mutations that result in undesired phenotypes, be controlled? What are the implications of eating genetically modified insects or animals on animals or humans? Will eradicating a whole species—even if it’s invasive or disease-carrying, like mosquitos or ticks—threaten the natural balance? Will altered creatures can live in natural settings, and if so, how long will they be able to do so?

Future prospects of Gene Drive

Gene drives offer a wide range of uses for limiting the spread of illnesses spread by insects, including malaria. Many other vector-borne illnesses, such as dengue fever, Lyme disease, and Zika, can be prevented in the same way. Early research has shown that gene drive technology can be used to target disease-causing fungus and reduce their capacity to change and become drug-resistant. It can potentially be used to regulate medication resistance mechanisms.

Gene drives also have far-reaching advantages for agriculture. It can, for example, be used to enhance total agricultural output by modifying weeds or lowering the prevalence of crop-damaging organisms. Other invasive species, such as rats, might be controlled via gene drives.

Gene drives hold enormous potential for disease preservation and the decrease of invading species once scientists have thoroughly addressed these problems. Scientists have already proven the efficiency of gene drives in species like fruit flies, mosquitos, and organizations all around the world are trying to create CRISPR/Cas9 gene drive systems. The future changes that gene drives will bring will be a thrilling journey!

Also read: Chloroplasts: The Rescuer from Pathogen Phytophthora infestans Invasion

Reference:

Buchman, A., Shriner, I., Yang, T., Liu, J., Antoshechkin, I., Marshall, J. M., Perry, M. W., Akbari, O. S., (2021). Engineered reproductively isolated species drive reversible population replacement. Nature Communications, 12 (1), 3281. DOI: 10.1038/s41467-021-23531-z

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