'zinc fingers' edit DNA; hope for AIDS, hemophilia, sickle-cell anemia and more

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In New Way to Edit DNA, Hope for Treating Disease

By NICHOLAS WADE in the nyTimes Published: December 28, 2009

Only one man seems to have ever been cured of AIDS, a patient who also had leukemia. To treat the leukemia, he received a bone marrow transplant in Berlin from a donor who, as luck would have it, was naturally immune to the AIDS virus.

If that natural mutation could be mimicked in human blood cells, patients could be endowed with immunity to the deadly virus. But there is no effective way of making precise alterations in human DNA.

That may be about to change, if a powerful new technique for editing the genetic text proves to be safe and effective. At the University of Pennsylvania, Dr. Carl June and colleagues have used the technique to disrupt a gene in patients T cells, the type attacked by the AIDS virus. They have then infused those cells back into the body. A clinical trial is now under way to see if the treated cells will reconstitute a patients immune system and defeat the virus.

The technique, which depends on natural agents called zinc fingers, may revive the lagging fortunes of gene therapy because it overcomes the inability to insert new genes at a chosen site. Other researchers plan to use the zinc finger technique to provide genetic treatments for diseases like bubble-boy disease, hemophilia and sickle-cell anemia.

In principle, the zinc finger approach should work on almost any site on any chromosome of any plant or animal. If so, it would provide a general method for generating new crop plants, treating many human diseases, and even making inheritable changes in human sperm or eggs, should such interventions ever be regarded as ethically justifiable.

Zinc fingers are essential components of proteins used by living cells to turn genes on and off. Their name derives from the atom of zinc that holds two loops of protein together to form a finger. Because the fingers recognize specific sequences of DNA, they guide the control proteins to the exact site where their target gene begins.

After many years of development, biologists have learned how to modify natures DNA recognition system into a general system for manipulating genes. Each natural zinc finger recognizes a set of three letters, or bases, on the DNA molecule. By stringing three or four fingers together, researchers can generate artificial proteins that match a particular site.
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We now have a full alphabet of zinc fingers, Mr. Lanphier said, but when we started the company it was like typing a novel with two fingers.

Zinc finger proteins have many potential uses. One is to link them to agents that turn on or turn off the gene at the site recognized by the fingers.

More powerfully, the zinc fingers can be deployed as a word processing system for cutting and pasting genetic text. Two sets of zinc fingers are attached to a protein that cuts the DNA in between the two sites matched by the fingers. The cell quickly repairs the break but sometimes in a way that disrupts the gene. This is the approach used in destroying the gene for the receptor used by the AIDS virus to gain entry to white blood cells.

Or, if DNA for a new gene is inserted into a cell at the same time as the zinc fingers that scissor the DNA, the new gene will be incorporated by the cells repair system into the DNA at the break site. Most gene therapy techniques use a virus to carry new genes into a cell but cannot direct the virus to insert genes at a specific site.
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Frank

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I'm always pessimistic about this new quick fix discoveries. Good for scientists but Pharma industry is so focused on $$$. :(
 
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Zinc Fingers Coincidence

Hi Guys,

OK, now this is too weird. Before yesterday I had never heard the term "zinc fingers". Then I came across the article below about ionic zinc. Today I see this post. I posted it here because I thought it was too much of a coincidence to ignore. :confused:

I don't know the first thing about this ionic zinc product, don't sell it, have never taken it, and am not recommending it. Anyone out there ever taken such a thing? They start talking about "zinc fingers" about 3/4 of the way down.

Take care,

Maxine




Ionic Zinc Free Spin Zinc Ions for Complete Cellular Absorption
by Dr. R. Gunderson & Scientific Researcher Ron Anderson

Dr. Gunderson's Ionic zinc is unique and different from all other zinc supplement formulas.

Many words are used within the healthcare community and many of those words are, or have become, generic. Words such as zinc, when used in most people's vocabulary, means nothing more than zinc. Zinc may mean a little more to a chemistry student who may categorize it as a transition metal having an atomic number of 30. History students may know that zinc was discovered in 1746 by Andreas Marggraf. But there is much more to zinc than this.

This led me-Dr. Gunderson-to do extensive research in ionics to prove there is more to the story of zinc as just mere words or categories that are all encompassing. Ionics involves ionization of minerals. It is the process of rendering an electrically neutral atom to an atom having a positive or negative electrical charge wherein the atom gains or loses one or more electrons or protons. When applied to plant-sourced minerals for use as a dietary supplement, the bio-availability of the minerals increases dramatically.

A few years ago I had the opportunity to meet with a person who developed a cough and throat lozenge from zinc gluconate-zinc salt of gluconic acid. I found this person's story both intriguing and stimulating. Some clinical studies had been carried out on his product with good results showing improvement in symptoms of coughs and colds.

I decided to investigate the results of his work and came up with some positive results and also some facts that concerned me. I observed a substantial beneficial change in the symptoms of colds with the people who took his product. The duration of infection was reduced.

What concerned me was that most people who participated in the studies needed to take large amounts of his lozenge product to achieve results. A stomachache was developed by the majority of people who took the amount required to reduce the cold symptoms and duration of infection. Observations of these studies inspired me to set a goal. The goal was to create a user-friendly product that worked more efficiently and without the side effects. I took into consideration recent research material that suggests the effect of zinc on colds may be influenced by the ability of the specific supplement formula to deliver zinc ions to the oral mucosa.

Also from my observations, and probably of more importance, I began to understand a fuller meaning of zinc. For there to be an improvement in the symptoms of coughs and colds, zinc had to have set off a kaleidoscope of regeneration information in the body leading to a cascade of biochemical reactions that assisted the rejuvenation of affected cells.

In my enthusiasm I set out to create the best possible product, which would be more effective and safe to use than any other product yet developed. This led to the development of my ionic zinc formula.

Zinc, the forgotten nutrient, is now a popular subject of clinical investigations.

Zinc is an essential mineral that is found in almost every cell of the body. It is responsible for many biochemical reactions in the body, stimulating the activity of over one hundred enzymes. Because zinc cannot be manufactured in the body it must be provided in our food or water diet or in zinc supplements.

A University of Florida study has shown that zinc may provide immediate protection against disease. The researchers observed an increase in genetic material in a very short time after taking zinc supplements. They conclude that part of the body's protective system is very sensitive to zinc and that zinc supplements can help fight infections and protect people against stress.

According to a Tufts University study, zinc is the number one nutritional deficiency in children in the U.S.A. Zinc enhances immune system competence and plays a vital role in fighting off colds and flue and facilitates cellular division and growth thus maximizing physical growth and development in children.

The immune system is adversely affected by even a moderate degree of zinc deficiency and totally depressed with a severe zinc deficiency. Zinc is required for the development and activation of T-lymphocytes-white blood cells the help fight infection. It has been clinically observed that T-cell lymphocytes increase in quantity and the ability of lymphocytes to fight infection improve in people with low zinc levels after taking zinc as a food additive. Zinc deficiency impairs many cellular, hormone and hormone-type immune functions including lymphocyte number and function.

Zinc is also known to promote healthy hair and facilitate wound healing and skin conditions, such as acne, eczema and psoriasis. It acts to prevent diarrhea, respiratory infections and pneumonia. Zinc interacts with chemicals to send messages to the sensory brain center and activates areas of the brain that receive and process information from taste and smell sensors. Therefore, zinc facilitates proper functioning of the ability to smell, taste and see. A zinc deficiency leads to dulling of the taste buds and ability to detect scents.

Zinc deficiency manifests clinically as growth retardation, hair loss, diarrhea, delayed sexual maturation and impotence, eye and skin lesions, loss of appetite, weight loss, delayed healing of wounds, taste abnormalities, and mental lethargy.

Some significant facts that should be noted with zinc.

1. Non-ionic forms of zinc are not as valuable to the body as ionic form as they do not go where they need to go.
2. Zinc in many forms, especially those that are chelated, can cause stomach problems.
3. The body can have difficulty metabolizing zinc to the ionic state thus making it less effective therapeutically.
4. Users gain maximum benefits from high quality zinc supplement products in the proper bio-available form.
5. Our research shows that zinc products are extremely effective when blended with our ascorbate method of production.

Looking at the problem of zinc absorption

Poor absorption of zinc is the prime cause of zinc deficiency.

The data generated throughout the course of a clinical study has been published in a book titled, "Cold Cure", by Michael Castleman. The data replicates the findings generated from studies conducted at our laboratory where the ionic zinc formula is produced.

Renowned health writer, Michael Castleman reached the same conclusion that we did, that zinc needs to be in ionic form to be effective. Berhon and Germonneaus who conducted the clinical study for Castleman proved that the dosage of zinc aspartate (aspartic acid)-a very common form of zinc-needs to be increased 1000 times to be more effective than Zn2+ ions or Dr. Gunderson's ionic zinc.

Berhon and Germonneaus also found that taken orally, zinc aspartate takes fourteen minutes to dissolve. Fourteen minutes dissolution time does not compare favorably to the instant dissolution of Dr. Gunderson's ionic form. Amazingly, Dr. Gunderson's ionic zinc is ready to be absorbed the moment it is taken.

Other forms of zinc, such as zinc gluconate, can cause stomach upset and can have poor after taste. It has been proven in our random study that zinc gluconate, which is the zinc of choice for inclusion in cold lozenges, causes mouth irritation and stomach upset. Of course when one has a cold, getting rid of the cold and not having to complain about the taste or bad mouth problem is preferential.

Another form of zinc is chelated. Minerals that are artificially bound to a compound such as nitrogen or an amino acid are called chelated minerals. They are chelated to protect them from interacting with other compounds and, supposedly, to assist assimilation of the mineral in the body. Depending on what the compound is, the chelated mineral may not be absorbed well and studies have shown no difference between chelated and non-chelated forms.

To understand assimilation of minerals in the body one must first understand how the body processes minerals obtained in food.

When food is consumed the body extracts the minerals, such as zinc, calcium and magnesium and then carries the minerals through the membranes of the intestinal tract. Digestive fluid in the stomach dissolves the (neutral electrical charged) minerals changing them into either positive or negative electrically charged ions. They enter the blood stream for transport to all parts of the body where they are needed. Finally, they are attracted to and pass through the cell membrane to be utilized within the interior cellular mechanisms.

During the digestive process, picolinic acid is secreted by the pancreas and enters the intestines. Picoinic acid helps to absorb and transport certain types of minerals and acts as a natural chelator in the body. It prevents positively charged mineral ions from being held tightly against the negatively charged membrane of the intestinal wall, allowing the mineral ion to pass through and into the interior cellular mechanisms.

This is all well and good providing that one has a healthy and efficiently working digestive system that allows for this natural bodily process. But the world is full of people suffering mineral deficiencies. One reason for mineral deficiency is a malfunctioning, ineffective digestive system due to low acid levels and disease and degeneration caused by sedentary living standards. If one's digestive system is malfunctioning and not able to process minerals correctly then sufficient levels of ionized minerals will not be forthcoming leading to the inevitable mineral deficiency syndrome.

The solution to a poorly functioning digestive system is to supplement the diet with minerals that are already in the ionized state, that is, minerals already having an electrical charge, either positive or negative. Supplementing the diet with mineral ions does not require the digestive system to create them.

Inadequate intake and increased losses of zinc from the body also result in zinc deficiency.

One of the many benefits of Dr. Gunderson's ionic zinc is that it contains ascorbic acid-vitamin C, a water-soluble vitamin-along with its two forms of absorbable zinc that have been shown to increase its effectiveness. Vitamin C is a life enhancer that must be renewed every day. Its most well known effect is to stimulate immune function and protect patients from colds and flu-like symptoms.

Zinc in its proper form has many health benefits. There are over 300 enzymes, including trypsin and alcohol dehydrogenase, that do not function without zinc as a cofactor.

The majority of zinc found in the body is contained within the muscles and bones and (in men) the prostate also benefits from high levels of zinc. The prostate gland holds higher levels of zinc than any other human tissue. Every time a male ejaculates, some zinc is lost which needs to be replaced through the diet.

Zinc works to protect against prostate cancer by inhibiting specific bindings of androgens, the hormones that are based on the structure of testosterone. Zinc has also been shown to inhibit the activity of 5-alpha-reductase, the enzyme that irreversibly converts testosterone to dihydrotestosterone (DHT). DHT is a male hormone in the body that is important early in the development of a man's life but surplus levels appears to be a cause of problems at other times.

The absorption of zinc in the proper form is critical as it enables the body to store the zinc in the correct places.

The thymus gland, located just under the sternum, controls some of our immune functions and is affected by the amount of zinc within our body. The thymus produces thymulin, a thymic peptide that is responsible for cell-mediated immunity.

As we age, the thymus gland diminishes in size and function. This has been observed in both human and animal studies and is considered a normal process. However, the state of zinc nutrition is also believed to play a part in thymus longevity. A zinc supplement given to aging mice restored the function of their thymus glands and led to the glands' regrowth. Researchers concluded that the usual involution (diminishing or shrinking) of the thymus gland is not inevitable and can be reversed with zinc supplements and reversed most effectively with instantly absorbed ionic zinc supplements.

Zinc is a vital constituent of polymerase, an enzyme required for the synthesis of DNA (deoxyribonucleic acid)-the genetic material of all cells-and many viruses, and RNA polymerase, an enzyme required for the synthesis of RNA (ribonucleic acid).

Zinc finger-like protrusions, called zinc fingers, contain zinc ions and extend from certain transcription factors, binding to the major wide groove of a DNA molecule. Some RNA and about 1% of DNA in the human genome require zinc fingers. With a zinc deficiency we are doing the DNA replication process in our body a disservice and could be causing unnecessary early aging that would otherwise be delayed.

A well known zinc finger transcription factor is WT-1 which is essential for the development of the gonads and kidneys.

Zinc, without question, is important to the body. Taking zinc in the proper "ionized" form, as demonstrated by Castleman, will safely take care of the body's needs without the side effects. Problems arise when high dosages of certain forms of "non-ionized" zinc supplements are taken that cause complications in the body. This can persuade a person to stop taking zinc altogether.

When I was involved in the AIDS research arena I had the opportunity to work with Dr. Jonas Salk. Scientists at the Salk Institute investigating zinc have discovered a link between low levels of zinc and cognitive impairment.

The study confirms what neuro-scientists have known for a long time, that zinc plays a critical role in human activity. It is now widely known that undernourished children suffering zinc deficiency have greater thinking ability and cognition after administration of zinc supplementation.

Brain health is desired by everyone which is a very a good reason to consume ionic zinc. The bio-activity level of ionic zinc is exponential when compared to other forms of zinc. We all want a good or even a better head on our shoulders and Dr. Gunderson's ionic zinc formula is a good head start.

Dr. Gunderson's liquid form of ionic zinc is very effective and simple to take orally. It is a product that is 100% absorbed by the body and most importantly is without side effects when taken as directed.

On completion of ongoing research and trials by clinicians at Dr. Gunderson's laboratory, more information will be brought forth regarding the positive affects of ionic zinc on the immune system and general well being of the body.

Summarizing the benefits of zinc.
An essential mineral that is found in almost every cell.
Provides immediate protection against disease.
Improvement in symptoms of coughs and colds.
Stimulates the activity of enzymes, which are substances that promote biochemical reactions in the body.
Supports a healthy immune system.
Promotes healthy hair and facilitate wound healing and skin conditions, such as acne, eczema and psoriasis.
Helps maintain your sense of taste and smell.
Essential element for DNA synthesis.
Supports normal growth and development during pregnancy, childhood, and adolescence.
Helps prevent pneumonia and diarrhea in children.
Works to protect against prostate cancer.
This brochure is PRESENTED for INFORMATION purposes only!
This brochure has not been evaluated by the FDA and is not intended to treat, cure,
mitigate, diagnose or comment on any from of medicine, medical therapy or medical help.
This brochure is for information purposes only!
 

determined

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This article in the NYT really blew me away. I have been following the progress of gene therapy clinical trials for years. This ability to specifically target certain sequences and disable them is HUGE. I will definitely be following the clincial trial for these AIDS patients.

Such amazing things are becoming possible. On this first day of 2010 I feel an odd combination of hope (the coming research/progress for CFS) and despair (much of the world's population does not have clean drinking water). I hope 2010 somehow provides help for all that need it.
 

MEKoan

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Hey If,

I just wanted to thank you for being such a good collector of interesting and pertinent medical info! There must be an actual word for that but I have no idea what it is :p

Anyway, fascinating but slightly scary piece.

Many thanks, If.