Future of Healing: Enveloped Delivery Vehicles for Targeted Genome Editing

Enveloped Delivery Vehicles for Targeted Genome Editing

 Enveloped Delivery

What are Enveloped Delivery Vehicles (EDVs)?

The innovation doesn’t stop there. The outer envelopes of EDVs can be adorned with multiple antibody fragments or targeting ligands, significantly enhancing their ability to home in on specific cell types. This targeting is achieved through the programmable display of antibody fragments on the surface of EDVs, which can recognize and bind to unique markers on target cells. This precision targeting ensures that genome editing occurs selectively in the desired cells, sparing the bystander cells in mixed cell populations both in laboratory settings (ex vivo) and within living organisms (in vivo).

Advantages Over Traditional Delivery Methods

Traditional viral vectors, such as the adeno-associated virus, have been limited by their evolved capsid tropisms, which restrict their ability to selectively target specific cell types. EDVs, on the other hand, leverage predictable antibody-antigen interactions to deliver the CRISPR-Cas9 machinery directly and selectively to cells of interest. This targeted approach not only enhances the efficiency of genome editing but also minimizes off-target effects, making it a safer option for therapeutic applications.

One of the most promising applications of EDVs is in the generation of genome-edited chimeric antigen receptor (CAR) T cells. By using EDVs to deliver CRISPR-Cas9 to T cells in humanized mice, researchers have successfully created CAR T cells capable of targeting specific cancer cells. This method offers a programmable, highly selective approach to cancer therapy, potentially overcoming many of the limitations of current treatments.

Broadening the Horizons of Therapeutic Genome Editing

The therapeutic potential of CRISPR-Cas9 has been widely recognized, but its application has been hindered by the lack of reliable methods for delivering genome editing tools to specific cell types. EDVs provide a solution to this challenge, enabling cell-selective genome editing with unprecedented precision. By displaying different antibody fragments on the surface of Cas9-packaging EDVs, scientists can target a variety of cell types within a mixed population, even those that are present in very small numbers.

This targeted delivery system has vast implications for the treatment of genetic disorders, cancer, and other diseases where cell specificity is crucial. As EDVs can be programmed to target virtually any cell type, they open up new possibilities for personalized medicine, allowing for treatments that are tailored to the individual genetic makeup of a patient’s disease.

Enveloped Delivery Vehicles represent a major advancement in the field of genome editing, offering a versatile and highly selective means of delivering CRISPR-Cas9 to specific cells. By harnessing the power of viral delivery mechanisms while overcoming their limitations, EDVs hold the promise of transforming the landscape of therapeutic genome editing. As research in this area progresses, we can expect to see an increase in the development of targeted treatments for a wide range of diseases, heralding a new era of precision medicine.


Wilson, R. C. & Gilbert, L. A. The promise and challenge of in vivo delivery for genome therapeutics. ACS Chem. Biol. 13, 376–382 (2018). – PubMed – DOI

van Haasteren, J. et al. The delivery challenge: fulfilling the promise of therapeutic genome editing. Nat. Biotechnol. 38, 845–855 (2020). – PubMed – DOI

Raguram, A., Banskota, S. & Liu, D. R. Therapeutic in vivo delivery of gene editing agents. Cell 185, 2806–2827 (2022). – PubMed – PMC – DOI

Stadtmauer, E. A. et al. CRISPR-engineered T cells in patients with refractory cancer. Science 367, eaba7365 (2020). – PubMed – DOI

Frangoul, H. et al. CRISPR–Cas9 gene editing for sickle cell disease and β-thalassemia. N. Engl. J. Med. 384, 252–260 (2021). – PubMed – DOI

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