Gene therapy.

The name sounds like a pleasant spaw treatment, but it’s actually a literal injection of genetically engineered viruses, designed to deliver genes right into your D N A. 

A virus is essentially just a Pro teen shell floating around, with a few genes and proteins inside it.

Each virus only attaches to a specific type of cell depending on its surface markers, and then hijacks that cell to make more viruses and spread really fast.

A virus is normally out there to harm you, but in the case of Gene therapy, scientists are scooping out the bad virus genes and putting in good genes instead.

The modified viruses are then injected into the patient so they can smuggle the treatment genes into our cells.

From then on, whenever the cell Repli Kate’s, our good genes are replicated along with the rest of the cell’s D N A . But wait! Doesn’t that sound dangerous?

Well, to know that, we will have to first understand how a virus even works.

Many of the viruses we are hacking are a special type of virus called a “Retro virus”. Which can be programmed to splice genes into your cells, a process they have spent billions of years of evolution to perfect.

Viruses have been around long before animals and might have even been the first type of life ever to exist on this planet, an idea called “the Virus world theory”.

It essentially means life didn’t evolve as a primordial soup of bacteria, but rather, as bits of genetic material smashing into each other until large viruses finally became Proto cells.

This ability to integrate it’s genes with other genomes, are what make the Retro virus work so incredibly well. 

A Retrovirus has 3 main parts.

First there’s the outer envelope, which lets it combine with the cell.

It’s made of a lipid bi layer, just like our cells are.

The proteins on the surface let it attach to a specific type of cell, the cell it wants to infect with the capsid, which contains the virus genes.

Second, there’s the virus proteins.

Proteins like Reverse transcriptase, which changes R N A into D N A, and Integrase, a protein that combines virus genes with the cell’s genome. And lastly, there’s the Retro virus genes.

2 Copies of R N A, which will eventually become part of the cell it infects.

As the virus comes close to a cell, it uses receptors exclusive to a particular type of cell.

For Example.

The CD4 receptor in immune system cells, which is used by the H I V virus to specifically infect white blood cells.

This causes the 2 membranes to combine, then the virus’s guts are released inside the cell.

Once the Retrovirus’s genetic material is injected inside, the Reverse Transcriptase protein converts the Virus R N A into single stranded human D N A. 

That same D N A is transcribed again into double stranded D N A, so that it could fit into our chromosomes.

The virus Integrase protein then carries it into the nucleus of the cell and inserts the gene into our genome, where it will be used just like the other D N A in the cell.

The virus gene will then code for instructions to start making copies of those virus proteins until it basically turns the cell into a factory for producing more viruses.

The Virus D N A messages are sent to the Ribosome and turned into receptor proteins.

Other virus genes code for capsid pieces to make countless new virus parts, which will be used to infect other cells.

This process will repeat until the virus is delivered to every cell in the body.

Overall, you can see why Retro viruses are so powerful.

They let you change billions of cells in the human body within a matter of hours.

Luckily, we can use this mechanism to our advantage when we fight aging and genetic disease.

It’s called “Gene therapy”. It treats genetic disease by providing copies of functional genes to make up for mutated genes.

If you have ever played literally any video game in the “resident evil” series, you are probably familiar with humans injecting themselves with viruses and delivering new genes into themselves.

New genes that either give them superpowers or turn them into zombies.

But these effects of gene therapy are certainly a bit exaggerated.

However, we have actually been studying gene therapy since the 19 80s as a way to correct biological defects, but only recently we realized that it can be used to treat aging as well.

The Senz foundation is currently using anti-aging gene therapy, with viruses that deliver backup copies of mitochondrial genes into our D N A.

This will let our cells function for longer and make new mitochondria when the old ones are killed by free radicals.

It’s essentially just genetic engineering for humans, except it’s done on living people rather than the embryos of designer babies.

Here is how it works.

We make the gene that we want to give to ourselves and package it into a harmless empty virus capsule.

This modified virus is called a “Vector”. The Vector acts as a transport vehicle for the gene we want to deliver.

Gene therapy is currently being explored as a treatment for many different diseases by delivering replacement copies of our genes in case the old ones get mutated. 

In fact, over 18 hundred clinical trials have been conducted to treat many different types of disease.

It can be used to fight cancer, blood diseases, Central Nervous system disorders, and immune system mutations. 

If you don’t already know, genes are segments of D N A that code for proteins.

Each gene produces a specific protein that helps the cell perform it’s specific function in the body.

Many diseases like Huntington’s disease, Sickle cell Anemia, and Cystic Fibrosis, are caused by mutated genes.

When a gene doesn’t work properly it provides incorrect instructions and causes the cell to make the wrong protein. 

If the cell is missing even one specific protein, it will cause a genetic disease. 

Gene therapy delivers a functional copy of this original gene into the patients cells, which will produce whatever proteins that the mutated gene cannot.

Vectors can be built using a type of Retro virus called a Len tea virus, or other viruses, like the A A V, which is a small simpler virus proven very safe for humans.

To make the vector, we remove the original genes of A A V, and replace it with the human genes we want to add.

Along with a promoter, which is a piece of D N A that lets us decode our gene.

More pieces of D N A called, “terminal Ree Pete’s”, allow the D N A to be packaged inside the virus.

The vectors will eventually enter all of your cells and deliver a copy of the functional gene into each one.

Once inside the nucleus, it will be absorbed into your chromosome and start producing the protein that you programmed it to produce, essentially treating whatever disease you want.

After we inject the vector into our bloodstream, the Virus particles containing our desirable gene begin to enter the small capillaries.

There are large pores in the capillary walls that it can use to get to our organs.

Our virus will then have to get past the macrophages, special immune cells which attack invading particles.

Lucky for us, some virus particles will escape the macrophages and arrive at the organ we want to treat.

Once the particle binds to the specific type of cell we want to change, the virus will merge with the membrane and take in our therapeutic gene.

After it finds a path to the nucleus, the virus proteins make sure the gene is incorporated into our genetic material.

Once it’s inside the D N A, the gene will help the cell function normally again and treat whatever disease it was suffering from.

Gene therapy was first tried on a young girl in the 19 90s and didn’t work as well as we’d hoped. 

Retro viruses reproduce often, so there’s lots of opportunities for mutation. 

However, we have worked out many of the problems in the recent years.

Gene therapy is experiencing a resurgence and we have started using it in experimental treatments again.

A gene therapy published in the Journal science has been used to treat Children born with Metachrome attic Luke O Disst row fee.

It worked by taking stem cells from the kids bone marrow and Re programming them with a genetically engineered Retro virus.

The Vectors binded to the stem cells and inserted the superior genes, replacing the stem cell’s mutated genes with copies of repaired ones.

They then injected those stem cells back into the children where they could multiply.

The children are now healthy, normal, and going to school.

Other studies have used it to treat immunodeficiency and leukemia using reprogrammed versions of the H I V virus. 

When gene therapy was used to treat 17-month-old Lay La Richards’ blood cancer, scientists hoped it could one day replace Chemotherapy.

Which is devastating to healthy cells and in some rare cases, might even do more harm than good.

But this new form of gene therapy inserts special genes into white blood cells which allow them to detect and kill tumors on their own. 

Another way is to use retro viruses to deliver a genetic self destruct button into the cancer cells.

When the gene is delivered and copied into protein, it causes the cell to kill itself at the molecular level.

Another way is to deliver a piece of junk D N A that inserts directly in the slots of the replicating genes, which basically jams up the cancer cell’s ability to divide.

This will stop the tumor from growing and make the cell healthy again.   

While gene therapy is great, it certainly isn’t perfect.

Here are 7 of the main concerns.

The first big problem is with the complexity of disease.

Gene therapy has so far only been used to treat very simple conditions where you only need to change one gene.

But it’s more difficult to treat complicated diseases which involve lots of different combinations of genes that either need to be added or deleted. 

There is also epigenetics, where the amount that genes are expressed needs to be amplified or toned down, but not deleted entirely.

The human Genome codes for over 20 thousand proteins and it will be a long time before we figure out how all of them work.

The second problem is public fear and politics.

We already have a rampant anti vaccine movement, so you can only imagine how people will react when we start injecting ourselves with re-purposed viruses.

The third problem is immune rejection.

18 year old Jessie Gelsinger died from multiple organ failure following a gene therapy trial at the University of Pennsylvania.

Scientists think it was because his immune system overreacted to the viral vector.

Another disaster with a french patient in 2003 led to a moratorium on gene therapy trials. 

The fourth big problem is targeting the gene to a safe location within the recipient cell.

Sometimes the virus might accidentally insert the gene at the wrong place, like right in the middle of another gene which could be important.

If the new gene splits an older gene into two pieces, then the gene won’t be able to code proteins and it could interfere with the processes of the cell.

This means that, while the virus has fixed the old mutation, it causes a new one by inserting into a more critical gene and ruining the  code. 

Despite these setbacks, we’ve rebuilt the reputation of gene therapy in the last 10 years. We now have improved gene silencing technology, Crisper Cass 9 gene editing technology, and Talen, which is how we treated Layla Richard’s Leukemia.

Even though we’ve dramatically improved the precision, there is still the fifth problem, the cost.

Even though biotech companies and investors are expecting to improve the efficiency in the next 10 years, a recently licensed treatment in the EU has a price tag of 1 million Euros per patient.

Luckily, the cost will go down when its mass produced.

The coming biotech era in the 20 twenties might see the price driven down dramatically to the point where we can start editing non disease related genes, like height, gender, and eye color.

Which brings us to the sixth problem, the problem of bioethics.

A Plasmid is a circular genetic structure in bacteria that can replicate genes independently of the chromosomes.

Plasmids are used in the laboratory manipulation of genes and can be inserted through a gene therapy process called Transfection.

While plasmids will never be able to adjust our genes to shoot electricity, like in the video game series Bioshock, it still raises many other questions.

Should people be allowed to genetically engineer themselves?

Can we add genes to increase attractiveness, strength, speed, or intelligence?

We are already getting close to that using what scientists call, “Schwart za negger mice”. These are mice that were injected with a gene to increase their muscle mass by 40%, which stayed forever, even as they aged.

Another study published at Princeton University genetically modified mice with a gene called NR2B.

The gene stimulates a receptor in the hippocampus, giving the mice increased intelligence, memory, and ability to learn.

Even better, the mice defied the aging process, as their cognitive function stayed the same as they got older.

Gene therapy is already producing glow in the dark mice, fish, and cats. This is done using the GFP gene taken from jellyfish and coral, which allows bioluminescence.

Who knows, you might even be able to purchase a glow in the dark pet one day. 

The last problem is the social implications of life extension. 

Organizations like Senz are already applying it to protect our mitochondrial genes and increase our life expectancy.

Using the work of Aging geneticists like Cynthia Kenyon, we could also potentially use it to extend our lifespan and block the aging process at the genetic level.

This is already being done by the BioViva Corporation, which believes in stopping aging at its molecular source. 

Bioviva is currently testing gene therapies to regenerate cells with the telomerase gene, a gene that repairs all aging damage done to a cell’s D N A when it divides.

The team is using a telomerase producing gene delivered by a well tested A A V vector undertaken by Maria Blasco’s team at the Spanish National Cancer Research Center, which has been shown to dramatically extend life span in mice.

In September 30th 2015, Bioviva announced that it was beginning its first human trial.

The C E O Elizabeth Parish, is so confident in her company’s medicine that she has agreed to be patient Zero, testing the virus on herself.

She believes that Aging as the root cause of all major diseases in the developed world, and thus, agreed to participate in the study herself, putting her life on the line.

However, research on curing aging is so controversial that the F D A did not allow it. Using Tee low mere gene therapy to try and cure aging is banned in the United States and the company had to do the study in Columbia instead. 

By 2016, some results of the study were showing to extend telomere length in Leukocyte cells from 6.2 kilobases to 7.3 kilobases. It also showed improvement in insulin sensitivity, an increase in muscle mass, and a more favorable blood profile.

However, some scientists suggest that telomere length measurements have low precision and the change is not significant enough. More studies will have to be done. 

The aging process is also poorly understood. Telomeres, despite being a large culprit of cell death, are not the only cause of aging.

Another problem with Telomerase gene therapy is that telomeres are a tumor suppressing mechanism and many aging scientists think we should be destroying telomerase genes rather than promoting them.

In summary, Gene therapy might be popular once again, but it is still in its infancy and has many problems to overcome.

Regardless, it holds the promise of many future prospects, ranging from cancer treatments to a cure for aging.

It is truly incredible, and has the potential to save millions of lives.

Who knows?

Maybe Gene therapy will revolutionize the way, that Evolution, interacts, with itself.

 

 

David Pye, Scientific Director of the Kidscan Childrens Cancer Research Charity, University of Salford

This article was originally published on The Conversation. Read the original article.

 

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