Summary of RNAi and its effectiveness against HIV


[HOME] BACKGROUND [RNAi] [Difficulties] [Terms] FEATURED EXPERIMENTS [RNAi vs HIV mRNA] [RNAi Combination Therapy] [RNAi Against Receptors] [RNAi by shRNA] [Computer Simulations] [SUMMARY] RESOURCES [Papers] [Websites] [Companies]	Summary HIV is one of the world's deadliest diseases. It has infected more than 40 million people (a number larger than the population of Canada). It not only ruins lives, but also takes away all hope of development in many third world countries. There is no cure for HIV. Current treatments provide only temporary solutions to the viral infection. When a drug is used against HIV, the virus lies low for a while, mutates, and comes back in full strength. The most common treatment is a time-varied cocktail of drugs known as HAART (Highly Active Anti Retroviral Therapy). HAART can prolong the onset of AIDS, but there comes a point where it becomes ineffective. A new method of treatment is needed. RNA Interference--a procedure based on a natural defense mechanism present within cells--might be the answer. Several capable researchers around the world have begun to study how RNA Interference might be used against HIV. "Proof of principle" studies have demonstrated the ability of RNAi (RNA Interference) to minimize viral reproduction in vitro. However, it remains to be seen how RNAi will fare in vivo. The road to the first RNAi based therapy will not be an easy one. Thus far, several difficulties (as outlined in the Difficulties section of this site) have been encountered. RNAi is highly specific with regards to its target. Since HIV evolves very fast, RNAi is limited to targeting highly conserved regions in the HIV genome. The quantity of siRNAs must also be carefully regulated. Too many siRNAs can set off an undesirable immune response. In addition to these difficulties, studies have shown that RNAi can silence genes that have not been targeted. The delivery of siRNAs (the main actors in the RNAi process) to infected cells also remains a major issue. Delivery methods will need to improve before RNAi is applied to humans. Although difficulties exist, RNAi does have some distinct advantages over traditional anti-HIV treatments. The main advantage is that RNAi is a natural cell pathway. A therapy that uses a natural pathway will have few side effects. The pathway's continued existence--from the prokaryote-eukaryote split to the present--is a testament to its effectiveness. Another advantage of RNAi is that siRNAs can be easily mass produced. This speeds up experiments, and could mean that future treatments involving RNAi will be inexpensive. RNAi can be used against a multitude of targets. As one can tell from the FEATURED EXPERIMENTS section of this site, RNAi can target HIV directly, or target the cell surface proteins that HIV needs to enter a cell. As more is discovered about the HIV life cycle, the number of possible targets for the RNAi process can only increase. Even if RNAi is focused on one target in a study, there are many ways in which it may be employed. Highly specific siRNAs targeting only conserved regions may be used, or various different siRNAs targeting several regions may be employed. RNAi can used as a mono-therapy, or may be combined with decoy RNA and ribozymes. RNA itself is a multi-talented molecule, and any therapy coming from it will be highly flexible and perfectible in nature. The author believes that the best method to pursue towards a treatment is that of inhibiting receptor expression. Stem cells can be removed from bone marrow, and receptor production in these cells can be inhibited by RNAi. The cells, when reintroduced to the patient, could fight HIV without becoming infected. In spite of its many advantages, it seems that RNAi might not have the necessary characteristics of becoming a complete cure for HIV. This is because 100% inhibition of the virus has never been achieved. No matter how diverse or targeted the RNAi process is, a small fraction of HIV mRNA eludes the RISC+siRNA complex. Even if the potential of RNA Interference as a cure might be limited, the author believes that its potential as a treatment for HIV is limitless. When the HAART drug cocktail has been sipped away by the virus, RNA Interference could continue the fight. The RNAi vs. HIV site was created in 2005 by Tim Baptist as a project requirement for BIOL3046 - A molecular evolution class offered by Dalhousie University's Biology Department. Tim Baptist is a 3rd year Biology Major at Dalhousie University. BIOL3046 is taught by Dr. Joseph Bielawski. Dalhousie University is located in Halifax, Nova Scotia, Canada. All questions and comments should be sent via electronic mail to Tbaptist@dal.ca.

BACKGROUND

FEATURED EXPERIMENTS

[SUMMARY]

RESOURCES

Summary

HIV is one of the world's deadliest diseases. It has infected more than 40 million people (a number larger than the population of Canada). It not only ruins lives, but also takes away all hope of development in many third world countries. There is no cure for HIV. Current treatments provide only temporary solutions to the viral infection. When a drug is used against HIV, the virus lies low for a while, mutates, and comes back in full strength. The most common treatment is a time-varied cocktail of drugs known as HAART (Highly Active Anti Retroviral Therapy). HAART can prolong the onset of AIDS, but there comes a point where it becomes ineffective. A new method of treatment is needed. RNA Interference--a procedure based on a natural defense mechanism present within cells--might be the answer.

Several capable researchers around the world have begun to study how RNA Interference might be used against HIV. "Proof of principle" studies have demonstrated the ability of RNAi (RNA Interference) to minimize viral reproduction in vitro. However, it remains to be seen how RNAi will fare in vivo. The road to the first RNAi based therapy will not be an easy one. Thus far, several difficulties (as outlined in the Difficulties section of this site) have been encountered. RNAi is highly specific with regards to its target. Since HIV evolves very fast, RNAi is limited to targeting highly conserved regions in the HIV genome. The quantity of siRNAs must also be carefully regulated. Too many siRNAs can set off an undesirable immune response. In addition to these difficulties, studies have shown that RNAi can silence genes that have not been targeted. The delivery of siRNAs (the main actors in the RNAi process) to infected cells also remains a major issue. Delivery methods will need to improve before RNAi is applied to humans.

Although difficulties exist, RNAi does have some distinct advantages over traditional anti-HIV treatments. The main advantage is that RNAi is a natural cell pathway. A therapy that uses a natural pathway will have few side effects. The pathway's continued existence--from the prokaryote-eukaryote split to the present--is a testament to its effectiveness. Another advantage of RNAi is that siRNAs can be easily mass produced. This speeds up experiments, and could mean that future treatments involving RNAi will be inexpensive. RNAi can be used against a multitude of targets. As one can tell from the FEATURED EXPERIMENTS section of this site, RNAi can target HIV directly, or target the cell surface proteins that HIV needs to enter a cell. As more is discovered about the HIV life cycle, the number of possible targets for the RNAi process can only increase. Even if RNAi is focused on one target in a study, there are many ways in which it may be employed. Highly specific siRNAs targeting only conserved regions may be used, or various different siRNAs targeting several regions may be employed. RNAi can used as a mono-therapy, or may be combined with decoy RNA and ribozymes.

RNA itself is a multi-talented molecule, and any therapy coming from it will be highly flexible and perfectible in nature. The author believes that the best method to pursue towards a treatment is that of inhibiting receptor expression. Stem cells can be removed from bone marrow, and receptor production in these cells can be inhibited by RNAi. The cells, when reintroduced to the patient, could fight HIV without becoming infected.

In spite of its many advantages, it seems that RNAi might not have the necessary characteristics of becoming a complete cure for HIV. This is because 100% inhibition of the virus has never been achieved. No matter how diverse or targeted the RNAi process is, a small fraction of HIV mRNA eludes the RISC+siRNA complex. Even if the potential of RNA Interference as a cure might be limited, the author believes that its potential as a treatment for HIV is limitless. When the HAART drug cocktail has been sipped away by the virus, RNA Interference could continue the fight.

The RNAi vs. HIV site was created in 2005 by Tim Baptist as a project requirement for BIOL3046 - A molecular evolution class offered by Dalhousie University's Biology Department. Tim Baptist is a 3rd year Biology Major at Dalhousie University. BIOL3046 is taught by Dr. Joseph Bielawski. Dalhousie University is located in Halifax, Nova Scotia, Canada. All questions and comments should be sent via electronic mail to Tbaptist@dal.ca.