Smart delivery for gene editing: ENVLPE enhances precision

Gene-editing technologies such as CRISPR/Cas9 are widely regarded as promising treatments for genetic disorders. However, one of the major challenges remains the reliable and safe delivery of these tools to specific cell types. 

“Previous viral and non-viral delivery systems such as adeno-associated viruses (AAVs), lipid nanoparticles (LNPs), and other virus-like particles (VLPs), have been valuable but face limitations,” says Dr. Dong-Jiunn Jeffery Truong. “ENVLPE directly addresses these issues while its modular design maintains compatibility with future gene-editing advancements.” 

• Use of engineered, non-infectious viral shells as delivery vehicles 

• Packaging of fully assembled gene editors 

• A protective molecular shield for vulnerable components 

• Compatibility with base editors and prime editors 

• Efficient intracellular assembly through redirected transport pathways 

In a collaborative study with UC Irvine, the ENVLPE system was tested in a mouse model with inherited blindness caused by a mutation in the Rpe65 gene. 

“The mice carry a disabling mutation in the Rpe65 gene, which is essential for producing light-sensitive molecules in the retina, and therefore are fully blind and unresponsive to light,” explains Samuel W. Du. After injection of ENVLPE into the subretinal space, the animals began responding to light stimuli. “The extent of restoration was astounding,” adds Julian Geilenkeuser. 

Compared to other systems, ENVLPE required more than ten times less dosage to achieve similar results. “We resolved critical bottlenecks and achieved a much more efficient packaging by the delivery agents,” says Niklas Armbrust. 

Beyond gene therapy for genetic disorders, ENVLPE also enables genetic modification of T cells for cancer immunotherapy. In cooperation with TUM University Hospital, ENVLPE was used to remove specific surface proteins from T cells to prevent immune rejection. This paves the way for universal T cells that are not restricted to individual patients. 

These advances support both: 

• In vivo gene therapies for inherited diseases 

• Ex vivo cell therapies for cancer 

Prof. Gil Westmeyer emphasizes: “The highly modular ENVLPE system brings us substantially closer to on-demand and precise genetic modifications of complex cellular models.” 

MEDICA-tradefair.com; Source: Helmholtz Munich