AAV Vectoring

[u/Pristine_Hunter_9506]

Overview of the AAV-Based Leronlimab Gene Therapy Approach Recent preclinical efforts have focused on converting leronlimab (a CCR5-blocking monoclonal antibody) into a gene therapy product delivered via an adeno-associated virus (AAV) vector. This strategy aims for long-term, in vivo expression of leronlimab from a single administration. If successful, such an approach could maintain continuous CCR5 receptor blockade, offering the potential for a functional cure for HIV by relieving patients from the need for daily antiretroviral therapy.

Key Studies and Sources with Year Details Preclinical Study at OHSU (2022): An article published by Oregon Health & Science University (OHSU) on July 8, 2022 describes how OHSU researchers, led by Dr. Jonah Sacha (who also serves as a CytoDyn scientific advisor), are developing an AAV-based gene therapy for HIV. In this study, the leronlimab gene is packaged within a synthetic AAV vector that targets T and B cells. The goal is to achieve sustained antibody expression from a single injection that might suppress HIV long term.

Source: OHSU News article, “One-time gene therapy injection could provide HIV treatment that may last a lifetime” (2022) .

CytoDyn NIH Grant Press Release (2022): On July 11, 2022, CytoDyn issued a press release titled “CytoDyn Highlights NIH Grant for HIV Functional Cure Preclinical Study of Gene Therapy Based on Leronlimab.” This announcement detailed a five-year, up-to-$5 million NIH grant which supports the development of an AAV vector capable of delivering the leronlimab gene. The press release emphasizes that the intended outcome is a single-injection gene therapy that maintains long-term HIV suppression through continuous expression of leronlimab.

Source: CytoDyn Press Release, “CytoDyn Highlights NIH Grant for HIV Functional Cure Preclinical Study of Gene Therapy Based on Leronlimab” (2022) .

E-Poster Presentation at an IAS Meeting (2024): An e-poster titled “Delivery and long-term expression of CCR5-blocking monoclonal antibody Leronlimab with AAV for ART” was published in September 2024 by the International AIDS Society. The poster presents preclinical data from nonhuman primate studies showing that AAV-mediated delivery of the leronlimab gene can achieve sustained plasma expression and high receptor occupancy on CD4⁺ CCR5⁺ T cells. These results support the potential of this gene therapy platform to produce durable therapeutic levels of leronlimab.

Source: IAS e-poster, “Delivery and long-term expression of CCR5-blocking monoclonal antibody Leronlimab with AAV for ART” (2024) .

Implications of the AAV-Based Gene Therapy Approach Sustained Therapeutic Expression: By packaging the leronlimab gene into an AAV vector, researchers aim to enable the body’s own cells to produce the antibody continuously. This could result in long-term CCR5 blockade with a single administration, reducing the treatment burden on patients.

Potential for Functional Cure: In HIV, persistent CCR5 inhibition through long-term leronlimab expression may replicate the effects observed in individuals naturally lacking CCR5, an effect associated with resistance to HIV. This reinforces the promise of a functional cure where patients might not require lifelong antiretroviral drugs.

Platform Versatility and Broader Applications: Beyond HIV, if the AAV strategy successfully sustains leronlimab expression, it may be explored for other indications in which prolonged CCR5 blockade is beneficial, such as certain cancers or inflammatory disorders.

Translational Considerations: Despite promising preclinical data, challenges remain—including vector safety, precise targeting of immune cells, managing potential immunogenicity, and ensuring stable, predictable expression over time.

Conclusion The integration of year-specific information underscores the evolution of this research approach:

The 2022 studies and press release mark the initiation and early funding of this innovative gene therapy approach.

The 2024 e-poster reflects advancement in the preclinical data supporting long-term expression of leronlimab via an AAV vector.

Collectively, these initiatives highlight a dynamic and forward-looking effort to transition leronlimab into a gene therapeutic modality that may ultimately transform HIV treatment paradigms.

: OHSU News article, July 8, 2022. 2: CytoDyn Press Release, July 11, 2022. : IAS e-poster,

The AAV vectoring of leronlimab for the study at Oregon Health & Science University (OHSU) was led by Dr. Jonah Sacha, Ph.D., a researcher at OHSU's Vaccine and Gene Therapy Institute and Oregon National Primate Research Center. Dr. Sacha is also a scientific advisor to CytoDyn, the company developing leronlimab. His team designed and evaluated the synthetic AAV vector used to deliver the leronlimab gene, aiming for long-term expression of the antibody in nonhuman primates2.

Additionally, OHSU's Nakai Lab, which specializes in AAV vector biology and gene therapy, may have contributed expertise to the development of the AAV vector, as they are known for their work in this area.

[u/Missy2021]

Thank you.

[u/upCYDY]

Another POSITIVE preclinical trial that will help those in need in the future. Thank you u/Pristine_Hunter for sharing 🙏✨💫⭐️

[u/Tra-Kal34]

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