Gene Editing has become one of the most promising areas in modern biotechnology, offering the potential to correct genetic mutations at their source. Tools like CRISPR/Cas9, base editors, and prime editing systems are opening new therapeutic frontiers in rare diseases, oncology, and regenerative medicine. However, the delivery of these gene editing tools into cells, especially in vivo, remains one of the biggest obstacles to clinical success.
Until now, viral vectors such as adeno-associated viruses (AAVs) and lentiviruses have been the most widely used vehicles for delivering gene editing systems. While these methods have advanced early clinical trials, they come with major limitations: restricted cargo size, immune responses, limited tissue specificity, and risks of genomic integration. Lipid nanoparticles (LNPs) and other non-viral delivery systems are offering a safer, more versatile, and scalable alternative.
In this blog, we explore how nanotechnology is addressing the critical shortcomings of viral vectors, and how next-generation nanoparticle platforms, like those developed at DIVERSA, are powering the future of gene editing therapies.
Why are not viral vectors enough?
Viral vectors have enabled key breakthroughs in gene therapy and gene editing, including FDA-approved treatments like Luxturna and Zolgensma. However, when it comes to delivering complex gene editing systems, especially multi-component CRISPR technologies, viral vectors show their limitations:
- Cargo size constraints:
AAVs can only carry ~4.7 kb of genetic material, while CRISPR/Cas9 systems often exceed that size, particularly when paired with regulatory elements or donor DNA templates. This severely limits the ability to deliver complete, functional gene editing tools. - Immunogenicity and pre-existing immunity:
Many patients have pre-existing immunity to AAV capsids, which can neutralize the therapy before it takes effect. Viral vectors can also trigger strong immune responses, reducing safety and preventing repeated dosing. - Genomic integration risks:
Lentiviral vectors integrate their payload into the host genome, raising concerns about insertional mutagenesis and long-term safety.
Manufacturing complexity and cost:
Producing viral vectors at scale is resource-intensive, expensive, and time-consuming. This can be a major hurdle for fast-moving gene editing programs, especially in rare or personalized therapies.
How does nanotechnology offer a better path forward?
Non-viral vectors, especially LNPs, are proving to be safer, more scalable, and more modular for gene editing delivery. Nanoparticles can deliver mRNA, guide RNAs, Cas9 protein or mRNA, and even DNA templates, all without integrating into the genome or triggering major immune responses.
Here is how nanotechnology addresses key limitations:
- Flexible cargo capacity and modular assembly
Nanoparticles can encapsulate large or complex nucleic acids, including Cas9 mRNA and guide RNA, in a single formulation. They can also be adapted for protein-RNA complexes (RNPs), used in high-precision editing strategies.
- Reduced immunogenicity and repeat dosing
Nanoparticles can be formulated with biocompatible lipids, reducing the risk of triggering harmful immune responses. Unlike viral vectors, they can also support repeat administration, which is often necessary in clinical protocols.
- Scalable and GMP-compatible manufacturing
Nanoparticle-based delivery systems are scalable using standardized formulation methods, making them compatible with Good Manufacturing Practices (GMP) for clinical and commercial use.
From a manufacturing perspective, non-viral delivery platforms, especially LNPs offer significant cost advantages compared to viral vectors. Producing AAV or lentiviral vectors involves complex cell-based systems, multiple purification steps, and strict biosafety requirements, resulting in production costs that can range from $1,000 to $10,000 per milligram of functional vector. In contrast, LNPs can be manufactured using synthetic, chemically defined components via scalable processes, with costs that are significantly lower per equivalent dose. These savings are particularly impactful for large-scale or repeat-dosing therapies, where viral production bottlenecks can delay development and inflate commercial pricing. Moreover, the GMP translation of nanoparticle systems is typically faster, allowing more flexible and affordable manufacturing pipelines for gene editing programs.
- Tissue Targeting with surface modifications
By modifying the surface chemistry of nanoparticles, adding ligands, antibodies, or peptides, developers can guide delivery to specific tissues, including liver, muscle, lung, or even brain. This opens possibilities for treating systemic and localized genetic conditions.
Gene Editing applications with nanoparticles in focus
Recent preclinical and clinical studies have shown how LNPs can deliver CRISPR components effectively:
- Liver-targeted editing using LNPs has shown promising results in transthyretin amyloidosis (ATTR) and hemophilia.
- Base editing therapies using LNPs are being developed for sickle cell disease and congenital metabolic disorders.
- Novel RNP delivery systems using LNPs are enabling highly efficient genome editing without relying on transcription in the cell.
This approach opens the door to gene editing for previously untreatable diseases, including rare genetic disorders, complex cancers, and even CNS-related conditions, as brain-targeting LNPs continue to evolve.
DIVERSA Technologies: advancing non-viral delivery for Gene Editing
At DIVERSA Technologies, we are developing advanced LNPs platforms tailored for the delivery of nucleic acids, proteins, and CRISPR systems. Our technologies offer:
- High encapsulation efficiency for mRNA, guide RNA, or Cas9 protein
- Customizable formulations for targeted tissue delivery
- GMP-ready production workflows suitable for clinical translation
- Low toxicity and high biocompatibility for sensitive applications
We collaborate with academic groups, biotech and pharma partners to accelerate gene editing programs from bench to clinic. Whether you are working on ex vivo editing, in vivo delivery, or base editing platforms, our non-viral delivery reagents provide a safer, scalable alternative.
Conclusion
Viral vectors have played a critical role in the first generation of gene editing therapies, but their limitations are becoming increasingly clear. Nanotechnology offers a new paradigm, enabling precise, transient, and tissue-specific delivery of gene editing systems without the risks of genome integration or immunogenicity.
With the ability to carry larger and more complex payloads, support repeat dosing, and scale for clinical use, LNPs and non-viral vectors are reshaping the future of genetic medicine.
At DIVERSA Technologies, we are proud to support the next wave of innovation, helping turn the promise of gene editing into clinical reality.
Visit www.diversatechnologies.com or send an email to info@diversatechnologies.com to explore our solutions.
References
Internal References
- Nanoparticles in Gene Therapy: A superior alternative to conventional transfection reagents
- Exploring the promise of Gene Therapy and the advances of mRNA-based approaches
- Nanomedicine prompts the development of CRISPR-Cas9 Therapies to treat hereditary angioedema
External References
- Wang, M. G. Z. X. Q., Glass, Z. A., & Xu, Q. (2017). Non-viral delivery of genome-editing nucleases for gene therapy. Gene therapy, 24(3), 144-150.
- Human Gene Therapy products incorporating human genome editing. FDA.
- Hejabi, F., Abbaszadeh, M. S., Taji, S., O’Neill, A., Farjadian, F., & Doroudian, M. (2022). Nanocarriers: A novel strategy for the delivery of CRISPR/Cas systems. Frontiers in Chemistry, 10, 957572.
