Mosquitoes Genetically Modified To Be Incapable Of Transmitting Malaria

Plasmodium falciparum enters erythrocytes and digests the haemoglobin before multiplying until the cell ruptures.

False colour Scanning Electron Micrograph

Scientists at the University of Californaia Irvine and the Pasteur Institute in Paris have successfully created a model of the Anopheles stephensi mosquito - a major source of malaria in India and the Middle East - that impairs the development of the malaria parasite. These mosquitoes, in turn, cannot transmit the disease through their bites. 

"Our group has made significant advances with the creation of transgenic mosquitoes," said Anthony James, a UCI Distinguished Professor of microbiology & molecular genetics and molecular biology & biochemistry. "But this is the first model of a malaria vector with a genetic modification that can potentially exist in wild populations and be transferred through generations without affecting their fitness." 

According to the World malaria report 2011, there were about 216 million cases of malaria and an estimated 655 000 deaths in 2010. It is currently the 15th most common cause of death in the world, with 91% of cases located in Africa.

James said one advantage of his group's method is that it can be applied to the dozens of different mosquito types that harbor and transmit the Plasmodium falciparum parasite, including those in Africa.

Anthony James and his team infected mice with the human form of malaria which caused the mouse to produce antibodies to the combat the parasite; They then exploited the molecular components of this mouse immune-system response and engineered genes that could produce the same response in mosquitoes. In their model, antibodies are released in genetically modified mosquitoes that render the parasite harmless to others. 

"We see a complete deletion of the infectious version of the malaria parasite," said James, a member of the National Academy of Sciences. "This blocking process within the insect that carries malaria can help significantly reduce human sickness and death." 

Comments:

Although the engineered genes could have been found in wild species of mosquito due to random genetic mutations, the time scale on which the prevalance of the gene would be widespread is debatable. Another concern is that the modification is passed on from generation to generation of mosquito, which could be seen as "playing God" with nature. Many wish to leave genetics alone as we have no right to interfere with nature.

Three-way IVF treatment to prevent mitochondrial disorders is deemed ethical

A Mitochondrion that produces energy by converting ADP to ATP.

The UK Nuffield Council on Bioethics, an independent UK ethics panel, today declared that a radical procedure involving 3 people to produce an embryo that has correctly functioning mitochondria, the energy producing parts of cells, was ethically correct to carry out.

Mitochondria have their own unique DNA separate from maternal DNA which is subject to mutations that disrupt the correct functioning and production of ATP.

The procedure, which involves genetic material from 2 women and a male, aims to replace the faulty mitochondrial DNA, which can cause muscle weakness, blindness and heart failure. The DNA from the mother and the father are put into another woman's egg which contains healthy, unmutated mitochondria. This fertilized egg is the implanted into the uterus as normal.

Dr Geoff Watts, who led the inquiry, said: "They could offer significant health and social benefits to individuals and families, who could potentially live their lives free from what can be very severe and debilitating disorders."

The Bioethics Council points out that just 0.1 per cent of the child's DNA would come from the donor. The impact on the characteristics of the resulting child from the donor would be so small it can be regarded as negligible, so it would be legally and biologically inaccurate to refer to such a donor as a "third parent".

Some critics that oppose the procedure state that it is akin to Frankenstein's monster being built out of parts from many different bodies and that it violates the norms of nature. Some believe that if this procedure is cleared for use in clinics it will create a slippery slope of unnecessary genetic modification and will lead to the fruition of "designer babies".

Another concern is that the outcomes of the procedure will last more than one generation and will be present in the modified child's offspring.

Combatting increasing resistance in bacteria

http://www.ted.com/talks/kary_mullis_next_gen_cure_for_killer_infections.html

Nobel Prize winner Dr Kary Mullis has been working on a method to counter the increasing prevalence of antibiotic resistant bacteria and the threat it poses by attaching antigens already recognized by the immune system to the bacteria so it is detected quicker and killed.

Alpha-gal epitopes, which are found in the tissue of other animals but not humans, are easily recognized as foreign and are broken down by phagocytosis in macrophages. Dr Mullis and his team had the idea to develop a method to attatch alpha-gal epitopes to pathogenic bacteria to flag the cell for destruction.

This was accomplished by creating an Altermune linker. This linker consists of the Alpha-gal epitope bonded to a DNA aptamer. The aptamer is a molecule that will latch onto a pathogen and stay there. This binds the epitope to the bacteria, making them one, which causes the bacteria to be engulfed and broken down when the epitope antigen is discovered by a macrophage.

The team have achieved success in proving that the concept works by experimenting with mice. Anthrax was given to the mice and an Altermune linker containing an alpha-gal epitope bound to a DNA aptamer with a complimentary 3D shape to a certain part of the anthrax pathogen. The result achieved was a 100% survival rate in the mice, where the control achieved a 0% survival rate.

Device may inject a variety of drugs without using needles

http://web.mit.edu/newsoffice/2012/needleless-injections-0524.html

MIT researchers have engineered a device that delivers a tiny, high-pressure jet of medicine through the skin without the use of a hypodermic needle. The device can be programmed to deliver a range of doses to various depths — an improvement over similar jet-injection systems that are now commercially available. 


The design is built around a small, powerful magnet surrounded by a coil of wire that’s attached to a piston inside a drug ampoule. When current is applied, it interacts with the magnetic field to produce a force that pushes the piston forward, ejecting the drug at very high pressure and velocity (almost the speed of sound in air, 240 m/s) out through the ampoule’s nozzle which is as wide as a mosquito’s proboscis. As the nozzle is so small, the breach in the skin is much less painful. The device can produce up to 100 mega pascals in as short a time as 1 millisecond.


This new system is better than current jet-injection systems as it can inject a wide range of volumes of drugs and at a wide range of speeds, as opposed to current systems which can only release the same amount of drug to the same depth every time. This means that the new system can be viable to use on a broader range of patients, such as children where less pressure is needed to breach the skin. With the ability to change the pressure on demand, it can be changed partway through the procedure allowing trans-dermal injections to be injected to the correct depth, i.e a high pressure to successfully breach the skin before dropping to a lower pressure to release the drug at the desired depth.

The team is also developing a version of the device for transdermal delivery of drugs ordinarily found in powdered form by programming the device to vibrate, turning powder into a “fluidized” form that can be delivered through the skin much like a liquid. Hunter says that such a powder-delivery vehicle may help solve what’s known as the “cold-chain” problem: Vaccines delivered to developing countries need to be refrigerated if they are in liquid form. Often, coolers break down, spoiling whole batches of vaccines. Instead, Hunter says a vaccine that can be administered in powder form requires no cooling, avoiding the cold-chain problem.

Article published May 24, 2012 by MIT News

Comments:

- The main difference between this new system of jet injector and currently available injectors is the high degree of customization which can lead to the tailoring of injection to a much more personal level.

- Another model of the same device is being developed that can vibrate, causing powders to behave like a fluid and to become viable for injection. This can solve the "cold-chain" problem in developing countries, where liquid vaccines must be refrigerated. As coolers break down, whole batches of vaccines are spoiled. If the vaccine is available in powdered form, no cooling is necessary, avoiding the cold-chain problem.