Project

Development of FIV Nanoblades as a genetic cure for feline immunodeficiency virus infection

Code
42Z04525
Duration
28 May 2025 → 27 May 2026
Funding
Funding by bilateral agreement (private and foundations)
Research disciplines
  • Medical and health sciences
    • Virology
  • Agricultural and food sciences
    • Veterinary microbiology
Keywords
FIV gene therapie
 
Project description

Today, 5–20% of the global cat population is living with feline immunodeficiency virus (FIV), the virus that causes feline acquired immunodeficiency syndrome (AIDS). This condition is characterized by increased susceptibility to opportunistic infections and malignancies. Like human immunodeficiency virus (HIV), FIV integrates its genome into host DNA, forming a persistent proviral reservoir in long-lived immune cells. Currently, no licensed antiretroviral drugs exist for FIV, leaving treatment primarily palliative. A curative strategy for FIV would require precise elimination of integrated proviral DNA from infected cells. CRISPR-Cas9 gene-editing technology has emerged as a promising tool to excise proviral DNA. Previously, I demonstrated this approach by developing novel CRISPR nanoparticles, termed HIV Nanoblades, that eliminate HIV infection in vitro and in vivo. These nanoparticles overcome limitations of classical viral vectors, such as low efficacy, prolonged Cas9 expression, viral mutational escape, and immune reactions. Here, I propose to develop FIV Nanoblades, virus-like particles with guide RNAs targeting conserved FIV genomic regions to eliminate proviral DNA from FIV-infected feline immune cells. First, the encapsulation of CRISPR-Cas9 ribonucleoproteins into FIV Nanoblades will be optimized. Next, the binding, uptake, and editing efficacy of FIV Nanoblades will be validated in feline immune cells. Finally, the ability of FIV Nanoblades to eradicate FIV provirus will be tested in FIV-infected cell lines and primary feline immune cells. This approach aims to eliminate the FIV reservoir while minimizing off-target effects and immune activation, offering a potential curative strategy for FIV.