The HIV-positive population continues to rise despite a worldwide decline in the rates of infection caused by human immunodeficiency virus (HIV).  The HIV virus continues to spread due to a lack of effective vaccines and pre-exposure prophylaxis methods, even though the availability and effectiveness of antiretroviral therapy has helped reduce acquired immunodeficiency syndrome (AIDS)-related deaths. 

RNA interference (RNAi) is a naturally occurring post-transcriptional gene regulation process that represses the expression of specific genes. Exploiting endogenous RNAi by externally-delivered small-interfering RNA (siRNA) is a promising therapeutic for the treatment of various diseases representing several major unmet medical needs. 

Development of successful HIV vaccine immunogens continues to be a major challenge.  Although gp120 was identified as having significant potential as a vaccine immunogen, attempts to elicit broadly neutralizing antibodies using recombinant gp120 failed.  The highly flexible gp120 may present numerous conformations to the humoral immune system that are not found on the viral spike.

Three-dimensional (3D) cell cultures systems are important for studying cell biology because they provide in vivo-like microenvironments more physiologically relevant than two-dimensional (2D) culture systems. In 3D culture systems, cells are grown in culture matrixes and turn into spheroids and organoids later processed for downstream analysis by microscopy and histology techniques. The processing of 3D cultures for analysis by microscopy or histology is laborious and time-consuming due to incompatibility of the 3D culture vessels and the microscopy and pathology blocks.

Human immunodeficiency virus (HIV) infections remain a pandemic, most prevalent in Africa and the Americas. Anti-retroviral treatments have been effective in preventing spread of the virus and active outbreaks of acquired immune deficiency syndrome (AIDS). However, the development and deployment of an effective vaccine would provide long-lasting protection and alleviate the need to depend heavily on prevention methods that require continued access and adherence.

RNA interference (RNAi) is a naturally occurring cellular post-transcriptional gene regulation process that utilizes small double-stranded RNAs to trigger and guide gene silencing. By introducing synthetic RNA duplexes called small-interfering RNAs (siRNAs), we can harness the RNAi machinery for therapeutic gene control and the treatment of various diseases.
 

Since its emergence in 2019, COVID-19 infected over 600 million people and over 6 million people have died from the disease. COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Neutralizing antibodies have been developed to bind to the receptor binding domain (RBD) on the spike (S) protein. Blocking the interaction of the RBD and the ACE2 receptor, is critical in neutralizing the virus. However, the S2 subunit, is also critical for viral infection and entry into human cells.

Papillomavirus pseudoviruses that comprise the L1/L2 capsid proteins can package a wide variety of non-viral DNA plasmids and deliver the packaged genetic material to cells. This function makes them attractive candidates as targeted gene delivery vehicles.

Adoptive T-cell therapy (ACT) utilizes tumor-reactive T cells to induce disease remission. While ACT has been used effectively to treat metastatic melanoma and certain epithelial cancers, most patients do not respond to treatment. Although the mechanisms underlying this variable response to therapy are not fully elucidated, the phenotype of the adoptively transferred cell is known to be a key determinant of treatment efficacy.

Researchers at the National Cancer Institute (NCI) have developed a method of stimulating an immune response in humans at risk for infection by, or already infected with, an Human Immunodeficiency Virus (HIV)-1 retrovirus. This method utilizes deoxyribonucleic acid (DNA) vaccines to stimulate CD8+ T cell immune responses. The DNA vaccine encodes antigens known to be effective against retroviruses, such as HIV-1gag, gp120, nefCTL, and proCTL. The same antigens are also expressed by the pox virus vaccine, which elicits an increased immune response when combined with the DNA vaccine.