Wednesday, June 2, 2010

Advances in Gene Therapy: A new generation of Antisense drugs may hold the key to treating our most debilitating diseases.

Gene therapy is the insertion of genes into cells and tissues to treat disease. The gene, which is a stretch of DNA or RNA, is injected into a vector -the delivery vehicle- such an Adenovirus: the virus (with a now modified DNA) is absorbed by a targeted cell, where the cell nucleus alters its proteins using the new gene. Although the technology is still in its infancy, it has shown great promise in treating diseases such as Cancer and HIV/AIDS, as well as deadly viruses.

Pushing modern technology even further, Antisense Therapy utilizes a synthesized strand of nucleic acid which bonds to the mRNA produced by a specific gene and inactivates it, in effect acting like a micro switch which can alter the way specific cells produce proteins or prevent them from reproducing.

Currently there are no available vaccines or therapies for Ebola. Antisense drugs are useful against viral diseases because they are designed to enter cells and eliminate viruses by preventing their replication. The drugs, which act by blocking critical viral genetic sequences, may be more potent than anti-virals such as protease inhibitors that seek to inhibit a protein needed for viral replication. In a new study using Antisense drugs containing called small interfering RNAs (siRNAs), researchers targeted the L protein which is critical for Ebola virus replication. Using a proprietary technology called SNALP, or stable nucleic acid-lipid particles, to deliver the therapeutics to disease sites in animal models infected with the most potent strain of Ebola they were able to effectively inhibit the growth of the virus in 3 out of 4 infected rhesus monkeys.

In cancer studies Antisense drugs have shown the ability to target the proto-oncogenes found in normal cells. These genes, when mutated or expressed at high levels, help turn a normal cell into a tumor cell. Other Antisense drugs can inhibit the protein kinase C-alpha, which signals the cell to divide in other cancers. Scientists have discovered a way to improve the effectiveness of antisense cancer drugs by attaching multiple strands of antisense DNA to the surface of a gold nanoparticle (forming an "antisense nanoparticle"). The DNA then becomes more stable and can bind to the target messenger RNA (mRNA) more effectively.

In HIV/AIDS treatment, researchers have been conducting clinical trials using a HIV lentiviral vector, which has the unique ability to integrate into the genome of non-dividing cells( other Retroviruses can infect only dividing cells). Because "short" antisense -such as ribozymes or RNAi- may be more likely to result in HIV strains that are resistant to the therapy, these new drugs contain a very long antisense that inhibits HIV replication and debilitates HIV's ability to resist the treatment. The antisense lies inactive in a patient’s white blood cells (specifically the CD4+cells), waiting for HIV to enter that cell. When HIV does enter, replication of HIV within that cell activates the vector, which then binds to and destroys the HIV.

Ongoing clinical trials are attempting to determine if patients can go off antiretroviral drugs permanently: while the data from this trial is still not complete, the results are very encouraging.

With the completion of the Human Genome Project draft in 2003, researchers have been given detailed knowledge of the human genome which will provide new avenues for advances in medicine and biotechnology. This information can provide a deeper understanding of the disease processes at the level of molecular biology, and will potentially determine many new therapeutic procedures.

Given the established importance of DNA in molecular biology and its central role in determining the fundamental operation of cellular processes, it is likely that expanded knowledge in this area will facilitate medical advances in numerous areas of clinical interest that may not have been possible without them.