A protein’s malfunction is the root cause of numerous diseases. Now, a team of researchers from Texas A&M University and Texas A&M AgriLife has found a way to quickly, efficiently, and briefly send a protein to the brain. This could have important medical and scientific uses. The protein delivery technique could be used in the future to treat spinal cord injuries and for a variety of other localized injections.
According to Jean-Philippe Pellois, Ph.D., professor and associate head for graduate programs in the Department of Biochemistry and Biophysics at Texas A&M College of Agriculture and Life Sciences, “We found that we could successfully deliver a protein into mouse brains.” “We’ve developed a trick to achieve this because proteins are big molecules that don’t easily enter cells or cross cell membranes.”
After serving its purpose, the protein and the delivery system both naturally degrade.
Pellois, who is also a researcher with Texas A&M AgriLife Research, said, “We wanted to make sure we had reagents that are very gentle on the cell, that can enter cells without disrupting them and then leave without a trace.”
Collaboration between Pellois’ lab and that of Cédric Geoffroy’s, a Ph.D. assistant professor in the Texas A&M School of Medicine’s Department of Neuroscience and Experimental Therapeutics, took place.
The National Institute of General Medical Sciences, the Cancer Prevention and Research Institute of Texas, the Craig H. Neilsen Foundation, and the Institute for Rehabilitation and Research Foundation were among the organizations that provided funding for the study.
The results of the study were published in the peer-reviewed journal Science Advances on September 28 under the title “In vivo peptide-based delivery of a gene-modifying enzyme into cells of the central nervous system.”
The workings of the protein delivery system
Proteins can have significant effects, so cells are selective about which ones they let in. The team’s plan to deal with this is like putting vegetables in mac and cheese to get a picky child to eat it.
According to Pellois, the endocytic pathway that cells possess is the equivalent of the digestive tract. “We are successful in getting our delivery method and proteins into a cell. The proteins can then enter the rest of the cell, particularly the nucleus, where we can cause a reaction after the delivery tool has been internalized in the endocytic pathway.
Other research facilities have found that the human immunodeficiency virus has a short peptide-like sequence of amino acids that cells prefer to ingest. The ability of that peptide to enter cells was further enhanced by the team. Once inside the cell, the peptide escapes the “digestive tract” of the cell, bringing with it the target protein.
People have combined a portion of this peptide with an intriguing protein, according to Geoffroy. “One step further is taken by our system. The majority of the protein will be delivered without modification. ”
The team discovered that their protein readily enters brain cells by combining the target protein and the peptide in solution and injecting the mixture into mouse brains. The mice were specially bred so that, if the protein arrived as intended, it would produce a visual signal called fluorescence. In fact, only after the protein and its delivery tool were injected together did brain cells nearby the injection site start to fluoresce.
According to Pellois, red fluorescent cells are created when the protein enters cells. So, we can tell if the protein has gotten in by looking to see if the cells have become fluorescent.
Implications for additional research
Geoffroy, an expert in neurotrauma and spinal cord injuries, says that the study shows that the approach works in a brain that is still working.
He stated that future research will concentrate on perfecting the technique to target just one cell type. The method’s current limitation of only supporting local injections is another drawback. The study does, however, pave the way for numerous potential applications.
According to Pellois, the use of this method for localized injections, such as those at the site of a spinal cord injury, is one important application. We are also considering the possibility of using this in the knee joints to repair cartilage or reduce inflammation brought on by conditions like arthritis.
Geoffroy claims that the approach could be used to deliver treatments other than proteins.
Additionally, it might make drug delivery more effective. This technique may result in a reduction in the dosage of a highly toxic anti-cancer medication that you are receiving, “said he.
On the elements of the method, Geoffroy and Pellois have filed a patent application. To move the research closer to applications, they also founded a company.
