Gene Therapy Development for HIV Infection
HIV is a subgroup of the Retroviridae family characterized by reverse transcription of the RNA genome and affects millions of people globally. The existing highly active anti-retroviral therapy (HAART) is efficient in slowing down disease progression but cannot eradicate the virus. With the major advances in biomedical research, gene therapy serves as an attractive alternative as it reconstitutes the immune system with HIV-resistant cells and can provide a potential cure. The HIV gene therapy approaches mainly focus on generating an immune system that is resistant to HIV in order to suppress viral replication. As a leading service provider in the field of gene therapy for years, Creative Biolabs can provide customers with a professional antiviral study platform including the advanced technical services and antiviral gene products. The RNA-based and protein-based therapeutics interferes with various stages of the HIV replication cycle by targeting cellular factors that are essential for viral replication but dispensable for the host, or by targeting viral factors.
Figure 1. The HIV replication cycle and examples of gene therapeutics (Falkenhagen 2018)
Potential Targets to Interfere with the HIV Life Cycle
There are several stages of the HIV life cycle including receptor binding, co-receptor binding, membrane fusion, reverse transcription, integration, replication, assembly, and budding. Human immune system is the main target of HIV infection. For instance, helper T cells (CD4+ T cells), macrophages, and dendritic cells. In addition, HIV infection leads to the loss of immune function and the development of AIDS. Currently, both small RNAs and protein agents have been used to target HIV replication and host factors.
Feature Services for Anti-HIV Infection Gene Therapy Strategies
- RNA-based Therapeutics
The first type of gene therapy products that can be employed to interfere with the HIV life cycle is the small RNA agent. There are mainly three types of small RNAs with different mechanisms of action to be used in HIV gene therapy: 1) the most common used are siRNAs that direct posttranscriptional gene silencing in a sequence-specific manner; 2) another group is the RNA decoys that function as "sponges" to sequester viral proteins and thereby interfere with viral replication; 3) RNA hammerhead ribozymes are the third agent for HIV gene therapy and these molecules cleave their targets in a sequence-specific manner and are capable of multiple turnover reactions. Creative Biolabs can design and operate many RNA-based gene therapeutics for our clients according to their requirements.
- Protein-based Therapeutics
Proteins or peptides can also be utilized to interfere with HIV replication or infection. It has reported that HIV-derived peptides and proteins have a potent effect in targeting viral entry, such as gp41-derived peptides can inhibit the fusion of the virus with the cell membrane. In addition, endogenous genes have also been utilized in HIV gene therapy because of their ability to confer innate immune defense against HIV infection. The retrovirus restriction factor, TRIM5α, was successfully used to suppress HIV-1 replication in a humanized mouse model. HIV therapy can also be accomplished by HIV-specific antibody mimetics, including single-chain variable fragments (scFv), antigen binding fragments (Fab), and engineered to recognize and neutralize HIV proteins.
Equipped with high-end technologies and Ph.D. level scientists, Creative Biolabs has exploited one-stop gene therapy development platform to meet your needs. Academic researchers in biotechnology can carry out the preclinical and clinical stage development of anti-HIV infection products by utilizing the various robust animal models and assay systems in-house. For more detailed information, please feel free to contact us. We will get back to you as soon as possible.
Reference
- Falkenhagen, A. and Joshi, S. (2018). Genetic Strategies for HIV Treatment and Prevention. Molecular Therapy - Nucleic Acids, 13, pp.514-533.
- Chung, J., Rossi, J. and Jung, U. (2011). Current progress and challenges in HIV gene therapy. Future Virology, 6(11), pp.1319-1328.
