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How Are Humanized Antibodies Made with Mouse Models?

How Are Humanized Antibodies Made with Mouse Models?

Humanized antibodies are antibodies produced in non-human animals. Humanized antibodies on production, if injected into humans, can cause damage due to variation in protein structure. These are altered earlier to become humanized.

The Necessity of Humanized Antibodies

Drugs are toxic substances and are effective when used in the appropriate dosage. However, due to the development of resistance, there is a demand for increasing dosage that is toxic to humans.

Most of the therapeutic agents are ineffective in treating various diseases.

In replacement for these therapeutic agents, antibodies are demanded. Among these antibodies, monoclonal antibodies are the best solution for passive immunity.

These humanized antibodies direly need to be produced for increasing human demands.

The Role of Mouse Models in Humanized Antibodies

Humanized antibodies are best to be generated in mouse models due to genetic similarities between humans and mice.

For example, monoclonal antibodies obtained from mice exhibit very little variation from human antibodies compared to antibodies originating from other animals.

Different Methods of Making Mouse Models

Sometimes lymphocytes of humans are fused with Epstein Barr virus or myeloma cells of the mouse to produce humanized antibodies.

But under few circumstances, the hybrid cells lose human chromosomes and become unstable. The effective ways to produce humanized antibodies are:

1. Recombinant DNA

 Recombinant DNA technology is mainly used to produce humanized antibodies.

The target gene involved in antibody coding is isolated and cloned in cells, mainly mouse cells. These mouse cells will act as antibodies-producing factories.

The target gene insertion and deletion in the mouse genome required alterations to produce the desired sequence of amino acids in antibodies.

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2. Chimeric Intermediate

The antibody (Fc) producing gene segment fused with the mouse antibody Fab portion to produce monoclonal antibodies in humans.

Such fusion is described as a human-mouse chimera. Mainly FC portion of the mouse antibody is replaced with the human antibody Fc portion for humanization.

The production of chimera selectively replaced the mouse antibody Fc portion with the human Fc portion. The amino acid sequences of the human Fc portion are altered by using genomic alterations tools.

In chimera, selective alterations are made in the Fab portion of the mouse that varies from the Fab portion.

The selective alterations are carried out in a way to maintain the integrity and specificity of antibodies.

The CDR region of the mouse Fab portion is never altered for selective binding of antibodies with target cells.

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3. Insertion of Relevant CDRs

The recombinant DNA technology can be used to produce humanized antibodies without intervening in the chimeric intermediates.

Following the production of antibodies in the non-human system, the DNA encoding antibody may be sequenced, and the CDR region of antibodies will be determined.

Now, a strategy can be developed to produce such CDR DNA sequence-based fragments along with antibody production. The linear DNA sequences are needed for this purpose.

The Value of Humanized Antibodies Techniques

1. CDR grafting

The complementarity determining regions (CDR) are hypervariable regions of antibodies and are responsible for the specific binding of antibodies with the target.

A humanization technique is CDR grafting, in which the CDRs of parental antibodies are carefully selected and grafted into the human framework to produce humanized antibody sequences.

2. Phage Display Technologies

In phage display technology, DNA-protein, protein-protein, and peptide-peptide interactions are studied through bacteriophage.

Further, a connection is generated in a protein molecule and gene-encoded. The epitope mapping is conducted, and ligands are isolated from phage libraries.

These are useful for drug design, validation of therapeutic efficacy of drugs, and development of a vaccine.

In addition, the phage display technology is used for the strategic applications of humanized antibodies in clinical cases as therapeutic measures.

3. Transgenic Mice

The mouse-generated humanized antibodies as a therapeutic agent have been impaired due to the inherent immunogenicity of these molecules.

The production of monoclonal antibodies with very low inherent immunogenicity involves the use of transgenic mice.

The transgenic mice express repertoires for human antibody gene sequences. Transgenic mice originated humanized antibodies exhibit high specificity and efficacy compared to others.

Conclusion

Cyagen provides humanized antibodies for research and commercialization point of view and is also providing the best transgenic mice model to produce highly specific humanized antibodies.

For more information, please visit https://www.cyagen.com/us/en/.

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NASA Switches Off Instrument On Voyager 2 Spacecraft To Save Power

Voyager

NEW YORK — To save power, NASA turned off another scientific equipment on its long-running Voyager 2 spacecraft.

voyager

NASA Switches Off Instrument On the Spacecraft To Save Power

The space agency announced on Tuesday that 2’s plasma science instrument, meant to study the movement of charged atoms, was turned off in late September to allow the spacecraft to continue exploring for as long as possible, which is estimated to be into the 2030s.

NASA turned off a suite of instruments on Voyager 2 and its twin, Voyager 1, after exploring the gas giant planets in the 1980s. Both are currently in interstellar space or the region between stars. The plasma instrument on Voyager 1 stopped working years ago and was finally shut off in 2007.

The remaining four instruments on 2 will continue to collect data on magnetic fields and particles. Its mission is to investigate the regions of space beyond the sun’s protective sphere.

NASA Switches Off Instrument On Voyager 2 Spacecraft To Save Power

It launched in 1977, is the only spacecraft to have visited Uranus and Neptune. It is now more than 12 billion miles (19.31 billion kilometers) from Earth. 1 is more than 15 billion miles (24.14 billion kilometers) beyond Earth.

SOURCE | AP

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Hurricane Kirk Could Cause Dangerous Surf Conditions Along The US East Coast

kirk

MIAMI — Hurricane Kirk’s waves could generate life-threatening surf and rip current conditions this weekend throughout the United States East Coast, as well as in Bermuda, the Greater Antilles, and the Bahamas, according to forecasters.

Kirk was a Category 3 hurricane in the middle Atlantic Ocean that might grow further but was predicted to stay away from land, according to the Miami-based National Hurricane Center on Thursday.

kirk

Hurricane Kirk Could Cause Dangerous Surf Conditions Along The US East Coast

Kirk-generated swells were forecast to reach parts of the Leeward Islands on Friday, Bermuda and the Greater Antilles on Saturday, and the East Coast and the Bahamas on Sunday, according to the center.

No coastal watches or warnings were in effect. The major storm was around 1,130 miles (1,820 kilometers) east of the Leeward Islands, with maximum sustained winds of 125 mph (205 km/h).

Meanwhile, Tropical Storm Leslie formed late Wednesday in the eastern Atlantic and is expected to strengthen into a hurricane in the following days, forecasters said. It was also not considered a threat to the land.

Hurricane Kirk Could Cause Dangerous Surf Conditions Along The US East Coast

The storm was about 540 miles (870 kilometers) southwest of Cabo Verde’s southernmost tip, with maximum sustained winds of 45 mph (75 kph), according to the center.

The storms raged in the Atlantic as rescuers in the United States Southeast sought for missing persons after Hurricane Helene struck last week, leaving a trail of death and devastation.

SOURCE | AP

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Giant Fossilised Footprint Of Dinosaur Found in China

Giant Fossilised Footprint Of Dinosaur Found in China

(CTN News) – A team of palaeontologists believes they have discovered fossilized footprints of one of China’s largest raptors. The collection of five fossilized dinosaur footprints is half the length of a school bus.

The footprints were discovered in a dinosaur trackway in south-east China in 2020. Scientists believe dinosaurs walked over the muddy river during the Cretaceous period, leaving footprints. Some footprints have been preserved for tens of millions of years.

The dinosaur trackway was unearthed in Longxiang and is around the size of a hockey rink. Some of the footprints are unusually formed, with intact imprints of only two toes.

Fossilised footprint of megaraptor found in China

Giant fossil footprints lead to megaraptor dinosaur discovery in China

Raptors, or predatory birds, are often small and referred to as deinonychosaurs. For example, a Velociraptor is around the size of a turkey. Few raptors, such as the Utahraptor and Dakotaraptor, increased in size significantly, reaching lengths of 5 to 6 metres. The Triassic ichthyosaur was the largest raptor known until now.

“Exploring Longxiang: The Rich Dinosaur Trackway in Southeastern China”

According to the scientists, the predator would have attacked its prey with a pair of huge “killing claws” on each foot.

What scientists discovered recently in China is massive, far larger than the largest superpredator known to date.

Scott Persons of the College of Charleston in South Carolina, and his colleagues, added another large raptor to the list. They named it Fujianipus, and they believe it lived in East Asia some 96 million years ago.

Scott Persons at the College of Charleston in South Carolina and his colleagues added another giant raptor to the list. They named it Fujianipus, and they say it lived in East Asia about 96 million years ago. Photograph:(Twitter)

Persons and his colleagues are currently working on areas of Fujianipus’ skeleton, therefore little is known. The investigators only discovered a few of its 36-centimetre-long imprints.

“Preservation conditions were right for footprints but not so great for bones,” Persons said. However, scientists are certain that the footprints belong to a raptor because each one contains the imprint of only two toes, which corresponds to the foot anatomy of raptors. Raptors generally have three toes, but they keep one off the ground to preserve the big claw at the tip from wear and tear.

People believe Fujianipus demonstrates that raptors had the ability to grow much larger and compete with the largest predatory dinosaurs on the landscape at the time – allosauroids, some of which exceeded 10 metres or more in length.

According to Persons, raptors had an advantage over allosauroids in terms of speed. However, without fossilized leg bones, the researchers cannot correctly measure Fujianipus’ speed.

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