Inject protein into the brain to toggle the switch of spinal cord repair

The origin of many diseases has a protein
that does not function properly.
Now, a multidisciplinary team of researchers at Texas A&M University and Texas A&M University has discovered a way to deliver proteins to the brain quickly, effectively, and briefly, with therapeutic and scientific implications
.
Potential future uses for the method may include repairing spinal cord injuries and other topical injection applications
.

"We found that we could successfully deliver a protein into the brains of mice," said Dr.
Jean-Philippe Pellois, a professor and associate director of the Department of Biochemistry and Biophysics in the College of
Agriculture and Life Sciences at Texas A&M University.
"Proteins are macromolecules that don't easily enter cells or cross cell membranes, but we've created a trick to make that happen
.
" Proteins and their delivery systems naturally degrade
when they come into play.

Pellois said: "We want to make sure that our reagents are very gentle on the cells, can enter the cells without destroying them, and then leave
without leaving a trace.
" Pellois is also a researcher at the Center for Agricultural Life Studies at Texas A&
M University.
Pellois and his lab collaborate with the lab of Cédric Geoffroy, Ph.
D.
, an assistant professor
in the Department of Neuroscience and Experimental Therapy at Texas A&M University School of Medicine.

The results, published September 28 in the peer-reviewed journal Science Advances, are "the delivery of genetically modified enzymes in vivo to cells of the central nervous system on a peptide-based basis.
"

Because proteins have a powerful effect, cells are very picky
about the proteins they allow to enter.
The method the team used to combat this situation was a bit like mixing vegetables in cheese macaroni to attract discerning kids
.

Pellois said: "Cells have endocytic pathways
equivalent to the digestive tract.
We are trying to get the cells to ingest proteins and our delivery tools
.
Once internalized in the endocytosis pathway, this delivery tool allows proteins to enter other parts of the cell, especially the nucleus, where we can trigger a response
.
”

Other labs have found that the human immunodeficiency virus contains a small amino acid sequence — a peptide — that cells prefer to ingest
.
The team further improved the ability of this peptide to
enter the cell.
Once inside the cell, the peptide escapes the cell's "digestive tract" and the target protein follows
.

"People have used part of this peptide for proteins of interest," Geoffroy said
.
"Our system goes a step further
.
You don't need to modify the protein – most of it gets delivered
.
”

The team found that the target protein and peptide were mixed in solution and then injected into the brains of mice, whose proteins easily entered brain cells
.
These mice are specially bred to produce a visual signal, fluorescence
, if the protein arrives as expected.
In fact, it was only after the protein and its delivery tools were injected together that brain cells near the injection site began to fluoresce
.

Pellois said: "If the protein enters the cell, the cell emits a red fluorescence
.
So, just by looking at whether the cell fluoresces or not, we can know if the protein has successfully entered the cell
.
”

Geoffroy, who specializes in nerve trauma and spinal cord injury, said the study provides the necessary evidence that this approach also works
in living brains.
Further work, he said, will focus on improving the method so that it targets only one cell type
.
Another limitation is that the method is currently only available for local injection
.
However, this research opens the way
for many potential applications.

"A key application is to use this method for local injections, for example at the site of spinal cord injury," Pellois said
.
"We are also investigating the possibility
of cartilage repair in the knee or fighting inflammation caused by diseases such as arthritis.
" Geoffroy said this approach may help provide therapies
other than protein.
"This can also enhance drug delivery
.
" If you have a very toxic anticancer drug, this approach can reduce the amount
we administer.
”

Geoffroy and Pellois have patented
components of this approach.
They also formed a company to bring the research closer to application
.

In vivo peptide-based delivery of a gene modifying enzyme into cells of the central nervous system