Helping CD4+ Cells Survive: Stealth Vectors, Antisense RNA, HIV/AIDS

HIV/AIDS is an increasingly severe worldwide problem. If the infected person can keep his CD4+ count high enough, he will probably not get AIDs. Anti-retroviral drugs have helped millions of HIV infected persons stave off AIDS, where the drugs are available, but a better method of restoring the CD4+ cell population is needed--one that does not require taking so many expensive pills on a daily basis.

Enzo Biochem has developed a "gene construct" consisting of three anti-sense genes, which are introduced into blood stem cells that are destined to become CD4+ T cells. These new CD4+ T cells will be resistant to the HIV retrovirus because the antisense genes they contain will neutralize the HIV gene products that are necessary for the virus to infect the cell. The more CD4+ T cells that survive, the less likely the person is to develop full blown AIDS.

Here is the report from Enzo Biochem (NYSE:ENZ):

In the upcoming trial, which is expected to get underway shortly, Enzo’s StealthVector® HGTV43™ gene construct will be used to transfer three antisense genes designed to interfere with the growth of HIV-1 into blood stem cells. These cells are expected to replicate and differentiate within the body of the HIV-1 infected individual to produce CD4+ T-cells, the main target of infection by HIV-1. The novel aspect of the current study is to increase the percentage of CD4+ cells that contain the anti-HIV-1 antisense genes with a protocol designed to partially reduce the patient’s blood stem cells before infusion of the engineered cells. The trial is intended to determine whether this procedure will create a supply of HIV-1 resistant CD4+ cells large enough to materially defer the disease progression of these HIV-1 infected individuals into AIDS

The Phase I study that took place at UCSF demonstrated the safety of the procedure and showed that the engineered stem cells were able to survive long term in vivo and to produce a low number of CD4+ cell progeny containing functioning antisense genes. Although there was no increase in the CD4+ cell count or reduction in the viral load, the yield of engineered cells has remained approximately constant over a number of years, in the case of one individual for as long as five years, supporting the conclusion that stable engraftment of anti-HIV-1 antisense RNA-producing blood stem cells occurred and the antisense genes continued to function.

....The HGTV43™ vector was developed by Enzo to include a proprietary delivery system designed to overcome a major challenge in gene medicine, namely the efficient and safe delivery of the medicine to the appropriate target. The benefits of Enzo’s “Stealth” vector technology are that it achieves efficient delivery of the genes into the patient’s cells, and that it is “silent” and unlikely to trigger an immune response. In addition, during the development of the vector two critical safety features were incorporated to minimize the possibility of inadvertently turning on deleterious genes in the subject.

“The Phase I trial demonstrated the safety of the HGTV43™ gene construct in 5 subjects and the ability of the engineered cells to survive and continue to function in vivo.

Read the full Enzo release here.
Hat tip medgadget.

Anti-sense RNA gene constructs are just one form of non-coding RNA. HIV/AIDS is such a complex infection, that it has been difficult for scientists to find the best way to attack it. Approaches to developing working vaccines have not been productive so far, but there is more than one way to skin this cat. Molecular biology has just begun to flex its muscles. Microbes, even HIV, do not stand a chance, in the long run--if.

If what? If western civilisation can continue to support its vast scientific research infrastructure. Given all the ongoing threats, that is not guaranteed.