RESUMO
Human immunodeficiency virus (HIV) is a lentivirus, a separate genus of the Retroviridae which are RNA viruses that integrate as DNA copies into the genomes of host cells and replicate intracellularly through various RNA intermediates. Several of these RNA molecules can be targeted by ribozymes and a number of investigators, including our group, have demonstrated the ability of ribozymes to suppress HIV replication in cultured cells. It is argued that the use of this ribozyme gene therapy approach for the treatment of HIV infection may act as an adjunct to chemotherapeutic drugs and may affect not just viral suppression, but also immune restoration. This approach can be tested in Clinical Trials, several of which are currently under way.
Assuntos
Terapia Genética/métodos , Infecções por HIV/terapia , HIV/efeitos dos fármacos , HIV/fisiologia , RNA Catalítico/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Sítios de Ligação , Ensaios Clínicos Fase I como Assunto , Desenho de Fármacos , HIV/patogenicidade , Infecções por HIV/virologia , Humanos , Técnicas In Vitro , Modelos Biológicos , RNA Catalítico/genética , RNA Viral/efeitos dos fármacos , RNA Viral/genética , Replicação Viral/efeitos dos fármacosRESUMO
Human immunodeficiency virus type 1 (HIV-1) is the primary etiologic agent for Aquired Immune Deficiency Syndrome (AIDS). HIV-1 is a lentivirus, a separate genus of the Retroviridae, which are complex RNA viruses that integrate into the genome of host cells and replicate intracellularly. Ribozymes are catalytic RNA molecules with enzyme-like cleavage properties, that can be designed to target specific RNA sequences within the HIV-1 genome. In addition to the genomic RNA, several RNA intermediates, including splice variants, can be targeted by a single ribozyme. We and others have demonstrated the ability of ribozymes to suppress HIV-1 replication in a variety of cultured cells. Ribozyme gene therapy for HIV-1 infection is a therapeutic approach that offers several potential advantages over conventional therapies in that it can potentially impact on both viral load and restoration of the immune system. Ribozyme gene therapy may be used as an adjunct to chemotherapeutic drugs, effecting viral suppression, and facilitating immune restoration without problems of patient compliance. Currently, an anti-HIV-1 ribozyme is being tested in two separate Phase I Clinical Trials.