These funky nanoparticles resemble viruses but work like life-saving medicines

The science behind the artificial virus

The study authors used bacteriophage T4 as a platform for their AVV project. They removed all the original genetic material from its protein shell(capsid) and then using CRISPR, they filled the bacteriophage capsid with foreign DNA and other biomolecules. 

The protein shell is then coated with lipids. In their recently published study, Rao and his team claim — this is the first time scientists have been able to coat bacteriophage T4 (containing foreign DNA) with lipid molecules. 

It’s a significant achievement because it allows an artificial vector to mimic natural viruses that also contain a lipid coating, and therefore, just like a virus, the AVV can also smoothly enter a human cell. “This is a major step forward to expanding the existing gene therapy space, and also creating a new space for future therapies and cures,” said Rao.

Interestingly, there are many other similar bacteriophages, but the researchers decided to go with T4 for creating AVVs because it has a stable capsid, a large external surface with 1,025 nonessential molecules, and a large internal volume that can hold up to 171 Kbp DNA, and nearly 1,000 molecules. 

Basically, the T4 platform enables the AVV to function as high-capacity nanoparticles capable of delivering large amounts of therapeutic biomolecules at once. The researchers also tested the artificial virus vectors in a lab environment to transfer dystrophin (the largest gene found in the human genome) into human cells. This experiment turned out to be a success.

T4-based AVV is possibly better than existing solutions  

According to the researchers, all the currently known gene-therapy vectors such as adenovirus or lipid nanoparticles are in the experimental phase. 

It’s actually very challenging to employ most of them as mainstream treatment technologies because they come up with “very limited load capacity, limited engineering and cell targeting capability, many safety concerns, and the complicated processes to produce these therapies are extraordinarily expensive,” said Rao.   

The CUA team claims that their T4-based artificial viral vectors don’t have any such limitations, and they represent a safe and practical gene therapy solution. However, this doesn’t mean doctors can start using the vectors immediately, further research is required to develop a treatment strategy that could fully utilize the potential of the AVVs.

“The actual therapy is years down the road, but this research provides a model for developing lifesaving treatments and cures,” Rao added.

The study is published in the journal Nature.

Study Abstract:

Designing artificial viral vectors (AVVs) programmed with biomolecules that can enter human cells and carry out molecular repairs will have broad applications. Here, we describe an assembly-line approach to build AVVs by engineering the well-characterized structural components of bacteriophage T4. Starting with a 120 × 86 nm capsid shell that can accommodate 171-Kbp DNA and thousands of protein copies, various combinations of biomolecules, including DNAs, proteins, RNAs, and ribonucleoproteins, are externally and internally incorporated. The nanoparticles are then coated with cationic lipid to enable efficient entry into human cells. As proof of concept, we assemble a series of AVVs designed to deliver full-length dystrophin gene or perform various molecular operations to remodel human genome, including genome editing, gene recombination, gene replacement, gene expression, and gene silencing. These large capacity, customizable, multiplex, and all-in-one phage-based AVVs represent an additional category of nanomaterial that could potentially transform gene therapies and personalized medicine.