Gene editing swats at mosquitoes

A new genetic tool may help wipe out Africa’s main malaria-carrying mosquitoes.  It’s known as a “gene drive.” In tests, it sterilized Anopheles gambiae mosquitoes. In other words, it kept them from reproducing.

A gene is the basic package of genetic instructions that tells cells how to build some protein. Proteins are the chemicals that do much of the work of cells. Gene drives are pieces of DNA that have been tweaked by scientists. These snippets of DNA have been designed to find a target gene, slice into it and then insert themselves. This cut-and-paste system alters the function of the original gene. And it is self-propagating, which means that it makes more of itself.

Other human-tweaked (or engineered) genes don’t reproduce themselves. A gene drive’s ability to make more of itself helps it get into more mosquitoes than would a regular inserted gene.

This is the second gene drive aimed at knocking out malaria. The first, announced two weeks earlier, works quite differently. It stops mosquitoes from transmitting the parasite that causes malaria. The newer gene drive instead eliminates the mosquitoes themselves by making it impossible for females to make new baby mosquitoes.

Scientists reported their achievement December 7 in the journal Nature Biotechnology.

Technique appears potent 

Most genes come in two copies. One copy comes from the mother. The other comes from the father. So each of a parent’s genes has only a 50-50 chance of getting passed on to a kid.

But like Star Trek’s Borg, gene drives become part of every unaltered target gene they encounter. These ambitious bits of DNA break standard inheritance rules. With the new technique, 76.1 percent to 99.9 percent of the offspring inherited the drive. As a result, the edited genes “drive” themselves quickly through populations.

Austin Burt first conceived of the idea for gene drives in 2003. This evolutionary geneticist works at Imperial College London, in England. For more than a decade, gene drives remained mostly just an idea. But this year, thanks to precision molecular “scissors” known as CRISPR/Cas9, four gene drives were put to use in several labs. These include the two in mosquitoes.

“They all work terrifically,” says George Church. He’s a geneticist at Harvard University in Boston, Mass.

Cas9 is a DNA-cutting enzyme borrowed from bacteria. Researchers can design genetic cousins of DNA — molecules known as RNA — to guide the enzyme to desired genes.

Not ready for prime time

Church is pleased to see that this latest mosquito gene drive works. Still, he says, further tweaks may be needed before it is ready for release into mosquitoes in the wild.

Researchers also may want to combine approaches. They might first release a gene drive that would prevent mosquitoes from carrying malaria. Later, they might release another to control mosquito reproduction, he suggests.

In the new study, Burt and colleagues first used CRISPR/Cas9 and another type of gene editor known as TALENs. These disrupted each of three genes that are very active in the egg-making organ of mosquitoes. Females carrying two copies of any one of the three disrupted genes were sterile. Once the researchers had confirmed that messing with these genes kept the mosquitoes from reproducing, the team then built gene drives to insert them into the genes.

Gene drives that interfere with reproduction make some people nervous. Such drives could make species go extinct. Many people would not miss mosquitoes. But no one really knows what getting rid of the insects might do to their ecosystem — the animals, plants and other living organisms in their neighborhood. For instance, some of those neighbors might rely on mosquitoes as lunch.

This gene drive also has some technical glitches. That means it won’t be the final version used to control wild mosquitoes. But the scientists are hopeful that future gene drives could cut populations of malaria mosquitoes dramatically, says study coauthor Tony Nolan. He’s a molecular biologist, also at Imperial College London. The public-health community needs new approaches for mosquito control, he says — “and this is a promising one.”

Power Words

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Cas9      An enzyme that geneticists are now using to help edit genes. It can cut through DNA, allowing it to fix broken genes, splice in new ones or disable certain genes. Cas9 is shepherded to the place it is supposed to make cuts by CRISPRs, a type of genetic guides. The Cas9 enzyme came from bacteria. When viruses invade a bacterium, this enzyme can chop up the germ’s DNA, making it harmless.

cell  The smallest structural and functional unit of an organism. Typically too small to see with the naked eye, it consists of watery fluid surrounded by a membrane or wall. Animals are made of anywhere from thousands to trillions of cells, depending on their size.

bacterium (plural bacteria)   A single-celled organism. These dwell nearly everywhere on Earth, from the bottom of the sea to inside animals.

CRISPR     An abbreviation — pronounced crisper — for the term “clustered regularly interspaced short palindromic repeats.” These are pieces of RNA, an information-carrying molecule. They are copied from the genetic material of viruses that infect bacteria. When a bacterium encounters a virus that it was previously exposed to, it produces an RNA copy of the CRISPR that contains that virus’ genetic information. The RNA then guides an enzyme, called Cas9, to cut up the virus and make it harmless. Scientists are now building their own versions of CRISPR RNAs. These lab-made RNAs guide the enzyme to cut specific genes in other organisms. Scientists use them, like a genetic scissors, to edit — or alter — specific genes so that they can then study how the gene works, repair damage to broken genes, insert new genes or disable harmful ones.

disrupt     (n. disruption) To break apart something; interrupt the normal operation of something; or to throw the normal organization (or order) of something into disorder.

ecosystem   A group of interacting living organisms — including microorganisms, plants and animals — and their physical environment within a particular climate. Examples include tropical reefs, rainforests, alpine meadows and polar tundra.

enzymes   Molecules made by living things to speed up chemical reactions.

evolutionary genetics   A field of biology that focuses on how genes — and the traits they lead to — change over long periods of time (potentially over millennia or more). People who work in this field are known as evolutionary geneticists.

gene   (adj. genetic) A segment of DNA that codes, or holds instructions, for producing a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.

gene editing    The deliberate introduction of changes to genes by researchers.

gene drive    A technique for introducing new bits of DNA into genes to change their function. Unlike other such genetic engineering techniques, gene drives are self-propagating. That means they make more of themselves, becoming part of every unaltered target gene they encounter. As a result, they get passed on to more than 50 percent of an altered animal’s offspring, “driving” themselves quickly into populations.

genetic  Having to do with chromosomes, DNA and the genes contained within DNA. The field of science dealing with these biological instructions is known as genetics. People who work in this field are geneticists.

genetic engineering   The direct manipulation of an organism’s genome. In this process, genes can be removed, disabled so that they no longer function, or added after being taken from other organisms. Genetic engineering can be used to create organisms that produce medicines, or crops that grow better under challenging conditions such as dry weather, hot temperatures or salty soils.

malaria   A disease caused by a parasite that invades the red blood cells. The parasite is transmitted by mosquitoes, largely in tropical and subtropical regions.

molecule (adj. molecular) An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O₂), but water is made of two hydrogen atoms and one oxygen atom (H₂O).

organ     (in biology) Various parts of an organism that perform one or more particular functions. For instance, an ovary is an organ that makes eggs, the brain is an organ that interprets nerve signals and a plant’s roots are organs that take in nutrients and moisture.

parasite   An organism that gets benefits from another species, called a host, but doesn’t provide it any benefits. Classic examples of parasites include ticks, fleas and tapeworms.

population  (in biology) A group of individuals from the same species that lives in the same area.

proteins     Compounds made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. The hemoglobin in blood and the antibodies that attempt to fight infections are among the better-known, stand-alone proteins.Medicines frequently work by latching onto proteins.

RNA  A molecule that helps “read” the genetic information contained in DNA. A cell’s molecular machinery reads DNA to create RNA, and then reads RNA to create proteins.

sterile     An adjective that means devoid of life — or at least of germs. (in biology) An organism that is physically unable to reproduce.

TALEN   An acronym for transcription activator-like effector nucleases. These are a class of enzymes that may be used as molecular “scissors” by some gene-editing processes.