A team of scientists from the Institute for Biotechnology and
Biomedicine at the UAB has produced an alternative to the use
of viruses in gene therapy. The researchers synthesised
nanoparticles which act as artificial viruses, capable of surrounding
DNA fragments and releasing them as therapeutic agents, with no
biological risk, into the interior of the cells.
Researchers of the Nanobiology Unit from the
Universitat Autònoma de Barcelona Institute of
Biotechnology and Biomedicine, led by Antonio
Villaverde, managed to create artificial viruses,
protein complexes with the ability of self-assembling
and forming nanoparticles which are capable of
surrounding DNA fragments, penetrating the cells and
reaching the nucleus in a very efficient manner, where
they then release the therapeutic DNA fragments. The
achievement represents an alternative with no
biological risk to the use of viruses in gene therapy.
Gene therapy, which is the insertion of genes into the genome with
therapeutic aims, needs elements which can transfer these genes to
the nucleus of the cells. One of the possibilities when transferring
these genes is the use of a virus, although this is not exempt of risks.
That is why scientists strive to find an alternative. With this as their
objective, emerging nanomedicines aim to imitate viral activities in
the form of adjustable nanoparticles which can release nucleic acids
and other drugs into the target cell.
Among the great diversity of materials tested by researchers, proteins
are biocompatible, biodegradable and offer a large variety of
functions which can be adjusted and used in genetic engineering.
Nevertheless, it is very complicated to control the way in which
protein blocks are organised, in order to form more complex
structures which could be used to transport DNA in an efficient
manner, as happens with viruses.
Professor Antonio Villaverde's group has discovered the combination
necessary to make these proteins act as an artificial virus and self-
assemble themselves to form regular protein nanoparticles capable of
penetrating target cells and reaching the nucleus in a very efficient
manner. In chemical terms, the key lies in a combination of cation-
peptide and hexahistidine placed respectively at the amino and C-
terminus ends of the modular proteins.
Researchers from the UAB have demonstrated that, when in the
presence of DNA, these artificial viruses surround it and carry out
structural readjustments so that the DNA is protected against external
agents in a similar fashion to how natural viruses protect DNA inside
a protein shell. Even the forms adopted by the resulting structures
seem to imitate virus forms.
"It is important to highlight that this ability to self-assemble does not
depend on the structural protein chosen and does not seem limited to
one particular type of protein. This provides the opportunity to select
proteins which could avoid any type of immune response after being
administered, which is of great advantage in terms of therapeutic
uses," Villaverde points out.
"These artificial viruses are promising alternatives to natural protein
nanoparticles, including viruses, given that their limitations, such as a
rigid architecture and a lack in biosecurity, can be less adequate when
used in nanomedicine," states Esther Vázquez, co-author of the study
and responsible for the Clinical Nanobiotechnology research line
within the Nanobiotechnology Unit of the UAB Institute of
Biotechnology and Biomedicine (IBB).
What occurs in chemotherapy as a cancer treatment can also be
compared to the problems in gene therapy. Conventional treatments
have an extremely high toxicity which limits their applicability. For
this reason, UAB researchers, in collaboration with Professor Ramon
Mangues from Sant Pau Hospital and Professor Ramon Eritja from
CSIC, are now adapting these artificial viruses to be able to transport
anti-cancer drugs directly to tumour cells. In this way, they will be
capable of releasing large therapeutic doses in a very localised
manner.
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