Creating virus-like particles for drug delivery

Many years ago, in the 1990s, we at the Molecular Biophysics Unit and the Department of Biochemistry of the Indian Institute of Science, Bangalore, determined the three-dimensional structures of two plant viruses. We are the only group working on structure of viruses in India so far. Only about a dozen laboratories across the world have deciphered the complete structure of viruses.

More recently, we used our understanding of the structure of the virus to create new virus-like nano-sized particles (VLPs) that can be used as carriers in a variety of applications, including drug delivery, vaccines, imaging and developing diagnostic kits.

Viruses are at the cusp of living organisms and inanimate matter. They possess genetic material but are unable to reproduce except when they are inside a susceptible host cell. Most of the viruses that cause diseases in animals and plants are relatively simple in structure. They have genetic material in the form of RNA or DNA that is covered by a coat or capsid made of protein molecules. After invading susceptible cells, viruses use the host cell machinery for their multiplication, causing disease.

Some plant viruses have the unique ability of penetrating several types of human cells. We do not fully understand how this penetration happens. Cells are generally impregnable to most macro molecules. It is this ability to penetrate the cells that makes some viruses potentially useful carriers of material which we may want to deliver into specific cells for different purposes.

It is here that our knowledge of the structure of viruses became very useful. We have cloned the coat-protein gene of sesbania mosaic virus (SeMV), whose structure was determined earlier, into a plasmid and expressed the protein in E.coli. Interestingly, the coat protein self-assembles to form VLPs that are non-infectious as they do not contain the full length viral genome. The coat protein gene can be genetically engineered to express foreign peptides such as those that can help in recognition of cancer cells or peptides that can bind specifically to antibodies, or peptides of other viruses for which vaccines are to be developed. These chimeric VLPs can be purified from E.coli in large quantities and used for structural studies as well as for medical applications. Recently, we have determined the structures of some of these VLPs.

These VLPs may be thought of as empty bags from which the genetic material has been pulled out leaving behind bits of cellular RNA. Instead of the genome, the capsid could be filled with dyes or drug molecules and used for imaging or delivery, respectively. Without the knowledge of the virus structure, we would not have known where exactly the peptide can be attached to the coat protein.

The chimeric VLPs can then be allowed to enter human cells. Unlike normal viruses, these VLPs do not carry any threat because plant viruses do not infect the humans, and in any case, they do not contain the full genetic material. These new nano-sized particles can therefore be used as nanocarriers for various medical applications such as targeted drug delivery, intracellular delivery of bound proteins, medical imaging, vaccine development etc.

We have demonstrated the possibility of such methods of delivery using the chimeric VLPs in our laboratory. Such biodegradable nanocarriers are being intensely researched in several laboratories all over the world. Some of them are in preclinical stage and may soon be part of medical diagnostics or treatment.