Gain of Function Research -Meaning and application of Gain of Function Research

By applying selection pressure to a culture, gain of function research means the repeated passaging of microorganisms to improve their transmissibility, pathogenicity, immunogenicity, and host tropism. This is done in a research setting to better understand how pathogens adjust themselves to the constraints in the environment.

Gain-of-function research is conducted to enable the planning of available measures to control diseases and the investigation of therapeutics and vaccines. To examine the influence of individual genes on protein expression and ultimately organism function, gene modifying technologies such as CRISPR can be used with selective serial passaging.

Gain of function (GoF) study improves or adds to an organism’s current properties. It might be a bacteria, rat, or fish that can be modified in the lab. It is known that a lot of people believe that GoF research entails how organisms are made to be more lethal, such as by boosting a virus’s ability to spread illness. That is a false perception. Sure, GoF research might result in a more hazardous creature, but that isn’t always the aim.

GoF research may be divided into two categories. Although viruses are used to exemplify GoF research, the ideas may be applied to any creature. One method involves the passing of a virus into a host until there is a generation of special features.

The type 2 Lansing strain of poliovirus, for example, has been adapted to multiply in mice and end up killing them. Although mice may not be infected by the Lansing strain, a study was able to create a new strain by passing the virus 99 times from mouse to mouse.

The virus’s latest form had a unique feature which can infect mice presently. Using recombinant DNA technologies to manufacture alterations in the organism’s genome is another technique to conduct GoF research. The recombinant virus created in this experiment has a unique feature: it could infect mice.

Our generation of poliovirus-susceptible transgenic mice is an example of how GoF may be done on mice. Mice may not be infected by the virus if it lacks poliovirus cell receptors. To make the mice become infected, one must pass the poliovirus receptor gene of humans in the germline of the mice, resulting in poliovirus receptor-producing animals.

This will make the transgenic mice become infected and suffer paralysis. This will make the mice develop a new trait that is susceptible to infection (poliovirus).

GoF research might yield a variety of valuable results. Do you wish to produce a beer with a unique flavour? Change one of the enzymes in the fermentation yeast. However, in the last 30 years, GoF research has gotten a terrible rap. A series of tests on highly virulent avian H5N1 influenza viruses served as the spark. Humans are seldom infected with these viruses, and they do not spread easily between people.

The virus was genetically engineered and passed among ferrets in trials to see what impeded transmission. As a consequence, a virus was created that could be transmitted between ferrets by respiratory droplets. These GoF tests were panned, which was unjustified because the passed viruses had lost their potency in ferrets! Nonetheless, an unjustified black cloud has lingered over everything since then.

Application of gain of function research

Commonly used in virology and has provided a wealth of information on the biological processes that underpin viral transmission and replication, the GoF studies are an integral part of scientific research.

Viruses with a high replication and mutation rate frequently produce escape mutants, which are lineages with modifications to their genome that reduce or remove the affinity of natural or vaccine-induced antibodies for the virus while having little effect on survival. The majority of viral changes are harmful to the virus’s function, although, in other circumstances, mutation can both increase virulence and improve immune evasion.

Prior to human trials, the FDA mandates animal testing for vaccinations. In situations where human viruses are being studied, however, strains capable of infecting the model species must be created because it is improbable that viral tropism for the model animal currently exists. Gain-of-function research allows for the identification of molecular determinants of transmissibility and the testing of vaccines in development.

Gain-of-function research, as previously mentioned, can highlight probable mutations in already known viruses, allowing for improved community surveillance, recognizing the time the changes occur, and giving room for the creation of vaccines in preparation for a future pandemic.

A virus may obtain a variety of mutations naturally, and they are not necessarily assured to show similar to those created by repeated passages in the laboratory. Likewise, anticipatory vaccine stockpiling is unlikely to be a significant benefit of gain-of-function research due to the high cost and time needed in vaccine manufacture and storage.

Any facilities doing gain-of-function research on highly pathogenic organisms should be transparent and safe, according to the scientific community. This is especially relevant in terms of public view in the aftermath of the COVID-19 epidemic, where public skepticism of science has been heightened by unproven conspiracy theories about SARS-origin. CoV-2’s.

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