The Power of Lentiviral Vectors in Modern Biopharma
Lentiviral vectors are a growing trend in biopharma. To further understand their place in the industry landscape, we define lentiviral vectors, discuss their current uses, and future outlook.
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In our previous article “Our Main Takeaways from 2025 ISCT & ASGCT New Orleans,” we discussed that lentiviral vectors (LVVs) are among the main emerging treatments our team is currently observing at trade shows. To create a better understanding of this subject matter, this week, we are taking a deep dive into LVVs, exploring their current impact, and looking to the future of their capabilities.
A Brief History of Lentiviral Vector Development
The discovery and characterization of Human Immunodeficiency Virus (HIV) in the early 1980s laid the foundation for our modern understanding of lentiviral vectors. In the mid-1980s, researchers expanded our understanding of the broader family of retrovirus vectors.
A few years later, in 1996, Italian physician Luigi Naldini, along with his team at the Salk Institute, discovered and demonstrated the ability to safely and efficiently create third-generation HIV-1-based lentiviral vectors. These vectors were designed with improved safety features, including the separation of viral components onto multiple plasmids and the use of VSV-G pseudotyping for broader cell tropism, significantly reducing the risk of generating replication-competent lentivirus (RCL).
Following this crucial development, lentiviral vectors saw widespread adoption in research settings throughout the late 1990s and early 2000s, becoming indispensable tools for stable gene delivery, RNA interference, and eventually for emerging gene editing technologies like CRISPR/Cas9.
The first human clinical trials utilizing LVVs occurred in the early 2000s, targeting a range of genetic disorders. Official success for lentiviral vectors emerged in 2017 in the United States, when the FDA approved Kymriah and Yescarta, CAR T-cell therapies that leveraged LVVs.
Understanding Viral Vectors
According to the National Cancer Institute (NCI) of the NIH, a viral vector is defined as “a form of a virus used to deliver genetic material into a cell”. Viral vectors are the broader category of which lentiviral vectors are a specific type.
There are other varieties of viral vectors, including adenovirus, herpes simplex virus, adeno-associated virus (AAV), and other types of retroviruses. The reason we sometimes use naturally occurring, existing viruses as viral vectors is that they have already become good at getting inside of human cells. This allows for much smoother delivery of genetic material.
The type of viral vector chosen depends on the disease it is treating and the cells that need to be repaired via the specific gene therapy. Below, we explore lentiviral vectors to understand the situations in which they are the best candidate.
What are Lentiviral Vectors?
Lentiviruses, like HIV, derive their name from the Latin word for slow, lentus. This is due to the fact that lentiviruses are slow-progressing and degenerative. Depending on the disease, it can take months, or even years between the infection of a lentivirus and the onset of symptoms.
Lentiviral vectors are a type of retrovirus that can infect cells, even if they are not in the process of dividing. This is because their outer shell acts as a protective layer, enabling their pre-integration complex to enter a cell’s nucleus where the DNA is stored.
They are created when scientists add the desired genetic material and viral components into “producer” cells, such as human kidney cells. What makes lentiviruses unique is that they can deliver new genes into body tissue that was previously challenging to alter on a genetic level.
LVVs have a high infection rate, and can be either integrating or non-integrating. A non-integrating LVV remains outside of the genome, while an integrating vector merges into the host genome, and will continue to be passed on to daughter cells.
Key Safety Features and Biosafety Levels
Not all lentiviral vector applications are the same; therefore, local IBC review and a complete risk assessment should both be conducted before working with LVVs. Generally, due to the ability of LVVs to transduce human cells, BL2 containment or enhanced BL2 containment are the recommended biological safety levels to implement in research or lab settings.
It is important that labs provide the proper education and protective equipment to staff when working with lentiviral vectors. One of the most probable routes for exposure risk is absorption through exposed abrasions, scratches, or needle-sticks on the skin. The other high-risk route for exposure is through mucous membrane exposure in the mouth, eyes, or nose. Less common, but still possible, is the risk of inhalation from aerosols.
In terms of patient safety, modern lentiviral vectors, specifically those that are third-generation and above, are engineered to be replication-deficient. This engineering significantly reduces the risk of unintended viral infections.
To prevent self-replicating vectors, or Replication Competent Lentivirus (RCL), lentiviruses are subject to thorough RCL testing before being cleared for clinical testing or other use. Additionally, key viral genes for replication have been removed from most third-generation and above lentiviral vectors, and self-inactivating (SIN) lentiviral vectors are being implemented for further risk reduction.
Companies Utilizing Lentiviral Vector Technology
Bluebird bio
Bluebird bio, a company leading the way in gene addition therapies, works primarily with lentiviral vectors. Their reasoning for this approach includes the range of severe genetic diseases they are able to target, as well as their design for single administration.
Across their various clinical trials, bluebird bio reports that they have treated over 170 patients with their investigative LVV therapies. They currently have three FDA approved lentiviral vector gene therapies, including Lyfgenia™ for the treatment of sickle cell disease, Skysona™ for cerebral adrenoleukodystrophy treatment, and Zynteglo® for beta-thalassemia treatment. All three of these treatments are ex vivo.
Orchard Therapeutics
Founded in 2015, Orchard Therapeutics focuses on treating patients affected by genetic and other severe diseases through gene therapy. They largely feature the use of lentiviral vectors in their hematopoietic stem cell (HSC) therapies and treatments. Additionally, they have noted that the generation of LVVs they use are self-inactivating, decreasing risk factors in their treatments.
In 2024, Orchard Therapeutics’ Lenmeldy™ was approved by the FDA for the treatment of children with pre-symptomatic late infantile (PSLA), early-symptomatic early juvenile (ESEJ), or pre-symptomatic early juvenile (PSEJ) metachromatic leukodystrophy (MLD).
Lentiviral Vector Manufacturing and Development
In addition to new treatments entering the market, some companies are looking at lentiviral vectors prior to research and development, providing them to other organizations for their treatments.
This helps to alleviate some of the stress on companies by ensuring LVV production is scalable, high-quality, and meets all safety requirements. Some companies leading the way in providing LVVs include Charles River Laboratories, and OriGene.
Applications of Lentiviral Vectors
As discussed above, the most important application of lentiviral vectors in modern research and development is their use in gene therapies. What makes LVVs a strong candidate for gene therapies are their ability to be used in both in vivo and ex vivo applications. To explore the difference between in vivo and ex vivo in-depth, visit our previous article “What is Cell & Gene Therapy?”.
Overall, the lentiviral vector's ability to transduce non-dividing cells make them a viable option for gene therapies targeting a wide range of rare and well-known genetic disorders. However, we are learning more about the potential applications of LVVs daily, and should continue to see their promise in a variety of application areas.
Future Directions and Emerging Technologies
According to Research and Markets, the global lentiviral vector market was valued at $201.8 million in 2023 and is projected to reach $713.3 million by 2032, with a CAGR of 15.1% during the forecast period. A major contributing factor to this expected growth is the development of new technologies to optimize manufacturing efficiency.
Lentiviral vectors are incredibly fragile, making them difficult to mass produce, transport, handle, and process. Not only does this slow down production, but it can make LVVs costly. Developments in manufacturing equipment are expected to increase scalability and alleviate cost.
Additionally, the cell and gene therapy market in general has been consistently growing, and is expected to continue to grow well into the future. This general market growth is beneficial to the success of LVVs.
Innovative Equipment for Life-Saving Therapies
Gene therapies utilizing LVVs have created treatments for some rare genetic disorders that were previously difficult, or even impossible, to treat. These developments are possible due to constant innovation within the biopharma industry.
To keep up with evolving industry technologies and trends, it is important to have reliable bioprocess equipment. At HPNE, a Getinge Company, we strive to ensure our product portfolio not only includes the highest-quality equipment, but also scales with your process as it changes.
To stay ahead in biopharma, you need to be adaptable. Our flexible equipment ensures that you can continue saving the lives of your customers and expand beyond your current treatments.
To learn more about our biopharma and biotech solutions, explore our full product portfolio, or reach out to our team of experts at info@hp-ne.com. You can also reach us by submitting a request through our contact us form.
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About HPNE
As the industry needs grow, High Purity New England, Inc. continues to supply the biopharmaceutical industry with a range of innovative products, from drug discovery and development to fill-finish, including their flagship product, custom single-use assemblies, as well as pumps, sensors, bioreactor systems, storage and handling solutions and other single-use solutions. Along with their own manufactured products for the global market, they are also a distributor for more than 18 brands in North America.
