Novel concept eyed for cure of AIDS Bioinformatics surfaces as revolutionary approach to medicine and cures

IF YOU ask almost anyone in Kuwait, they wouldn’t know it, but bioinformatics has recently surfaced as a potentially revolutionary approach to medicine and cures. Bioinformatics is a novel approach to finding cures for certain diseases using a combination of computer science and microbiology, which works on identifying, targeting and/or (de)activating certain DNA which is responsible for certain diseases, such as HIV/AIDS.

Bringing this research concept to Kuwait is Yousef Aleneze. Although having only recently graduated from Loyola University Chicago, his research at various universities and organizations has already led him to theoretical breakthroughs. This has included work with the NAACP on finding the potential technology that may lead to an HIV cure. Yousef is currently proposing a research concept regarding finding a cure for HIV at the KU Faculty of Medicine, using certain novel concepts that have not yet been undertaken on a global scale.

His research has been academically published at the International Conference on Molecular Epidemiology and Evolutionary Genetics of Infectious Disease, and has research experience in various fields, including ovarian cancer and malaria, amongst others.

Question: Tell us a little about yourself, your background, etc.
Answer: My name is Yousef Aleneze and I am a bioinformatics analyst. I am working on creating new bioinformatics & proteomics computational workflow systems to analyze essential biological macromolecules and antigens.
Furthermore I will incorporate a de novo fragment based drug design part in the workflow system. The next project after that is automated candidate drug manufacturing based on genomic and proteomic information of infectious pathogens.
Bioinformatics is a new discipline where you marry computer science and microbiology where you decipher the DNA that are responsible for certain diseases. You can also use bioinformatics to target different pathogens. Pathogens are microbes that cause disease. One of the main problems with pathogens, especially viruses, is that they mutate a lot, so we have to figure out the logic throughout the computation behind the mutation; is there a specific pattern that we can target to pretty much corner viruses from mutating into super-bugs.

Q: Tell us about your research, in some detail.
A: I have research experience in Loyola University Chicago and the University of Washington, on two different topics. In Loyola I did some research behind finding new ways where we could defend ourselves against the most resistant forms of malaria through a technique called biomimetics, which is using biology and nature as a model for designing new devices, processes or techniques to resolve health problems that we have.
At the University of Washington I did some bioinformatics analysis with cervical cancer and breast cancer to figure out if there are any differences between certain genes being regulated upwards or downwards, and how we could switch them off and on to decrease tumor growth.

Q: Specifically, what research have you done in HIV/AIDS?
A: Regarding HIV, the way I started was through the National Association for the Advancement of Colored People (NAACP). I got assigned as the Health Committee Chair. One of the main initiatives was to increase HIV awareness, so I decided to take it a step further and said, why can’t I contribute my education to actually find a solution for this. One of the main issues with HIV is you hear the term treatment a lot. When it comes to treatment, this comes with financial undertones. Unfortunately, because of the demographics of HIV, large portions don’t have the funds to actually get the treatment, so here came the quest for a cure to end this pandemic.
What I did was actually read my microbiology books and read chapters that we hadn’t taken, for my general knowledge, and try to see the flaws in HIV. That is, what things it depended on, and how could we manipulate that to actually inhibit the HIV from getting to those needs. While it took some time, I decided to focus my senior project on creating a computer program that would actually analyze how HIV mutates throughout time, through a bioinformatics technique called philogenetics. You actually draw a timeline, and each timeline has a node and each node shows which part of the HIV changed. This gave us potential targets to attack, and inhibit HIV growth. While that was a success and I got officially published in the International Conference on Molecular Epidemiology and Evolutionary Genetics of Infectious Disease in New Orleans, this past November.
We figured out that this was not enough to actually cure HIV because HIV has found a way to hide from medication in a very stealthy manner. So, let’s say you have drugs attacking infected cells, HIV, through evolution, found a way to switch off its processing or transcription. When you look under a microscope, it would seem like they’re normal cells, and once you stop the medication, it spikes up again. That problem is called HIV latency.

So we had to figure out ways in which we could wake up the HIV cells and force them to reactivate. That caused difficulties because a lot of the chemicals that activate HIV are toxic, so we had to figure out ways in which we could have a non-toxic analogue of those compounds to activate HIV.
With my new specific technique we decided to look further into nanotechnology because they’re cost-effective, easy to make, non-toxic and they have the ability to actually answer cells without inducing a new response. Ultimately it’s a stealth process. With that, you can add specific functionalities and options within these nanoparticles were they can be responsive to certain stimuli. So if I want a nanoparticle to attack a tumor cell, I can add something on the surface of the nanoparticle which binds to the specific tumors of the electronic target and would deliver the jerks that I want to deliver for the drugs to inhibit the tumor growth or drugs that would cause that specific cell to die. So rather than chemotherapy, you selectively choose the tumor cells, leaving the healthy cells intact.

Q: What are the main developments that have occurred in nanoscale research and cures?
A: Overall, there have been big advancements in terms of reactivating latent HIV, because that’s one of the biggest obstacles that we’ve had. Several studies in the US (Stanford University to be specific) designed synthetic analogues of this chemical called bryostatin, which is a chemical found in marine protozoa in very minute amounts.
So minute that you would need 18 tons of this protozoa to make 8 grams of bryostatin. The extraction was not very cost effective, so they had to figure out a synthetic way, and once they did they found out that the synthetic analogue was much more potent and active in HIV than the natural product itself.
Now, we figured out how to activate the HIV. Now we have to figure out how to react to HIV. To complete the strategy, we have to figure out how to kill those specific cells that have the HIV, and how to inhibit HIV infections to other healthy cells.

There were two techniques that I used. One of the techniques that I computationally used was the nanoparticles, but one of the main concerns was what target I should use to activate those nanoparticles.
These nanoparticles are going to go to all white blood cells, so I had to figure out a way where I would trick the HIV into opening this package and releasing the drug that would actually kill the affected cell. If you want to put it into perspective, it’s like sending a letter bomb that only HIV can read, and that bomb will self-destruct without causing any harm.
Another thing is, let’s say that HIV managed to avoid the “explosive” and starts to spread, the HIV particle itself contains these long “limbs” that bind to white blood cells - CB4 cells to be exact. We had to figure out a way to cut off these arms. This can be done through catalyc antibodies.
Unfortunately many of the previous studies have focused only on antibodies that bind to these limbs - these surface proteins - , but HIV also managed to change its structure to a very flexible confirmation which would let the antibody latch-off. Rather than bind them together, we need to destroy these surface proteins so they can’t be used again.

Q: Do you have the statistics on AIDS in Kuwait vs. worldwide?
A: The statistics on AIDS in Kuwait according to UNAID state there are 214 Kuwaitis with AIDS. AIDS is not a major concern in Kuwait, but it’s a major global concern because every day 1,000 children are born with aids. 60% of them die before the age of 2. so it’s not targeted towards Kuwait only, it’s more of a global mission towards ending such a terrible enemy. But I am aiming to put Kuwait on the map in terms of the research and in terms of investing some effort in figuring out world problems.
The reason why I want to work in Kuwait is because it’s bigger than me. I definitely want this to be a patriotic moment. I think that would actually put Kuwait in one of the leading positions in terms of biotechnology.

Q: How do you evaluate the current level of awareness on potential nanoscale cures in Kuwait?
A: It’s quite low, not many people know about it because I don’t think there’s a lot of media exposure on nanotechnology. Most of the technological exposure in on consumer products rather than industrial or clinical technology. That’s one of the main issues that we have. One of the main problems that we have is that young scientists don’t have enough media exposure.
However, I have spoken to Professor Abusalem Mustafa who is the Vice-Dean of Research in postgraduate studies, and the Director of the Research Core Facility at Kuwait University, and I have emailed him about my research proposal. He seemed interested and decided to schedule a seminar to speak at Kuwait University.
 

Q: Realistically, how long do you think it would take to implement this kind of knowledge in Kuwait and globally?
A: Honestly speaking, since it’s based on a clinical study, it would probably take a decade, because we have to make sure that this technique doesn’t kill people, because we’re dealing with lives, and the number one asset of every human being which is health. Pre-clinical studies will probably take 2-3 years.
Clinical studies might take an extra 10 years, but nevertheless if we find certain results for clinical studies, that still puts us in the top rankings in terms of latest findings and research towards taking the first steps to finding a cure for HIV/AIDS.
On a global scale, many companies have gone through clinical trials. In clinical trials you have phases. A lot are doing the first phase, which is testing to see if it’s toxic or not. The main issue is that we don’t know, because I don’t think any HIV drugs have gone to phase 2. Phase 2 is testing whether the drug does cure HIV or not.
With that being said, for a drug to go from the lab to the market, it will probably take 10-15 years. So our time frame is the same on the global scale. They might be a couple of years ahead.
Just to make it clear, many researchers are aiming towards finding a vaccine rather than a cure. I honestly don’t think vaccines are going to work because HIV still finds a way where it can infect other cells in novel ways.
For example, there was a recent video where HIV infects different cells by forming a bridge, which is a new mechanism that we haven’t studied yet, between the infected cell and uninfected cell. So the tradition vaccine strategy using antibodies is going to be ineffective.

Q: What kinds of tests have been conducted, and with what results?
A: I can remember one off the top of my head, and it’s VRC-01. That’s a vaccine which was proven to neutralize the majority of different substrates of HIV. The only problem is it does not solve the problem of the internal transfer of HIV genome data from infected cells to uninfected cells. We have to infiltrate the cells rather than look at it in a vast spectrum and immobilize it. We have to attack the infected cells, because these are the reservoirs of HIV.

Q: What are the potential benefits of nanoscale cures over other types of cures?
A: One of the things is that it’s very easy to make industrially. You’re dealing with manipulating particles with such a tiny structure, they can do things larger structures can’t, in terms of stability, stealth, responding to specific stimuli, and toxicity. It’s not very toxic.
You can manipulate these structures in many different ways to do different tasks. In a nutshell, it’s four things; the cost, east to synthesize, low toxicity and being able to actually select specific targets.
Also, when you are dealing with organizing chemicals in a nanoscale, they gain super physiochemical properties. They can have a super solubility, mechanical, electric and magnetic effect. We will use these advantageous properties to infiltrate HIV’s offense tactics and act upon it.
 

Q: Is it just AIDS that you’re trying to cure, or could nanoscale technology potentially be developed to cure other types of illnesses?
A: One of the main viruses is hepatitis, especially hepatitis C, there’s no cure for it. Using a similar technique, there are also novel techniques by which we can cure hepatitis C.
Nanotechnology can also be used for a new generation of antibiotics, since the current antibiotics have been ineffective due to multi-drug resistance, such as MRSA, TB - which is the second cause of death after HIV. Since nanoparticles are inorganic chemicals, dealing with metals, bacteria particles could not be resistant to them, because they can’t manipulated the structure of non-antibiotics.

I actually unintentionally worked on finding potential therapy for malaria. The whole concept behind that was that we were trying to analyze the lining of the mosquito that carries the malaria. We were trying to figure out the biological structure of that lining - that is how come the malarial parasite does not affect the mosquito? Can we apply a similar biomimetic strategy to defend ourselves from malaria. So we were using the mosquito’s structure as a model to defend ourselves.
We actually sub-cloned a domain called GPX. GPX is actually responsible for defending a mosquito from being infected by the parasite that it carries. For now it’s still in-vitro. The principal investigator of this project still hasn’t gone to the next stage.
 

Q: What are the main obstacles currently in the way of implementing the theory practically?
A: One of the main concerns is the stability of the nanoparticles, and whether the nanoparticles could actually absorb into the target cells that we expressly want to target through endocytosis. Another concern would be if the stimuli-responsive mechanism would be fully effective. Would it actually deliver to the target that would actually malfunction halfway through. These are the main precaution we had to take to minimize errors. We used computer simulations and quantum molecular mechanics and quantum chemistry to figure out the optimal structure for the design of the nanodevice.

biography

Yousef Aleneze is a bioinformatics analyst currently working on implementing his research proposals in Kuwait. He has conducted research on nanotechnological cures for HIV, as well as malaria and other illnesses.

By Joana Saba - Arab Times Staff


By: Yousef Aleneze

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