Human immunodeficiency virus is well known for its ability to cause the fatal disease AIDS. But, today the advanced technology and the ever increasing brain power of scientists have brought out the positive side in the most deadliest virus. Yes, its true! now HIV is not so evil. It is surprisingly impressive to know that HIV can be used for human benefit. I know that it is hard to believe but this virus can actually be used to treat diseases. HIV proves to be a good vector in gene therapy; exploring this new method has been the work of many scientists and labs all over the world. We can say that it is the future face of disease treatment.
First, what is gene therapy? It is the modification of genetic material of a living cell for therapeutic purposes. It involves the insertion of a functional gene or another molecule that contains an information sequence into a cell to achieve therapeutic effect. In simple words, if there is an absence of a gene which codes for a specific function in our body, we incorporate a similar sequence pattern in the DNA which would carry out the same process and the disease can be treated. You may like to imagine it this way, that in the future, this technique may allow the doctor to treat a disorder by just inserting a gene into a patient’s cells instead of using drugs or surgery! The transfer of the information is carried out by a vector; retroviruses, a type of viral vectors commonly used as a tool to deliver genetic material into the host cell as it infects the cell.
HIV belongs to the Lentivirus genus of viruses of Retroviridae family. And this genus of viruses can be used as vectors. The most significant characteristic feature that enables them to become a highly efficient tool in therapy is their ability to both work with dividing and non – dividing cells. Non dividing cells refer to the terminally differentiated cells for example-neurons, macrophages, hematopoietic stem cells, retinal photoreceptors, and muscle and liver cells, cell types for which previous gene therapy methods could not be used. Lentiviruses are the only type of virus that are diploid; they have two strands of RNA. Thus, HIV contains a diploid single stranded positive sense RNA-genome that is approximately 10k b(base pairs) long. The ends are flanked with long terminal repeats (LTRs). A Psi-sequence is found near the 5’ end of the RNA-genome which is necessary for packaging viral RNA into virus capsids to continue the infection of HIV in its host (Schmidt, The HIV Page). However, the HIV’s genetic information is integrated into the DNA of the host cell, so its RNA must be converted into DNA inside of the host for viral replication to be successful. This is done by reverse transcription of the RNA into DNA, and some of the proteins described.
Reverse transcriptase synthesizes the first strand of DNA from the RNA template, and the host DNA polymerase synthesizes the second strand to produce dsDNA. LTRs also serve as part of the promoter for transcription of the viral genes (Schmidt, The HIV Page). Thus, the virus is protected from attack by the immune system. It is this ability of HIV to integrate its genetic material into a host cell that scientists would like to harness to put towards gene therapy. It has been shown that the HIV vector has an even higher rate of expression in its hosts’ cells than other retroviruses. Also, HIV gene therapy vectors do not trigger immune reactions, making them very attractive delivery systems .
There still remains the risk of using a viral vector in gene therapy for their ability to express themselves and cause the disease. As a repercussion there can be insertional mutagenesis and might lead to cancer or leaukemia. This concern remained theoretical until gene therapy for ten SCID-X1 patients using Maloney murine leukemia virus resulted in two cases of leukemia caused by activation of the LMO2 oncogene due to nearby integration of the vector. On the brighter side, this vector has been successfully used by scientists in their experiments to cure many diseases such as metabolic diseases, cancer, viral infection, cystic fibrosis, muscular dystrophy, hemophilia, retinitis pigmentosa, and maybe even Alzheimer’s disease (Adler, Gifford, and Sumner; Naldini et al.; Amado and Chen, 1999; Planelles). Research for the development of these procedure is going on. It surely holds a future promise for this therapy to be used extensively.
As the saying goes, “Where there is a will, there is a way”, it is a no-brainer that scientists may have found a way to make lentiviral vectors more safe. HIV lentiviral vectors are being produced whose packaging plasmid does not contain the necessary HIV genes. By using non-human lentiviruses, scientists hope to bypass the issue of host infection by the gene therapy vector.
So, let us hope that scientists ‘will find a way’ to make this technique more safe and that it can be used successfully.
Image Credit: Dino H
Adler, K., J. Gifford, and R. Sumner. HIV as a Vector in Gene Therapy. [Online.]
http://wwwpp.uwrf.edu/%7Ekk00/hivvector/hivvector.htm. [12-13-99, last date accessed.]
Amado, R. G. and YI. S.. Chen. 1999. Lentiviral Vectors—the Promise of Gene Therapy Within Reach? Science. 285
CFAR: Center for AIDS Research at UC San Diego. Last update 10-18-99. Lentiviral Vector Core. [Online.]
http://hsrd.ucsd.edu/Cfar/lenti/lenti.html. [12-13-99, last date accessed.]
Goldman, M. J., P. Lee, J. Yang, and J. M. Wilson. 1997. Lentiviral Vectors for Gene Therapy of Cystic Fibrosis.
Human Gene Therapy. 8: 2261-2268.