New DNA Nanotechnology Particle Testing Technique Developed

Diseases such as cancer, Parkinson’s disease, and HIV/Aids, and even inherited disorders such as cystic fibrosis and hemochromatosis all have one thing in common; they have no known cures. However, with gene therapy, this may soon change. DNA Nanotechnology is used in gene therapy in a process whose purpose is to treat or prevent a disease using genes.

More specifically, the process delivers therapeutic nucleic acid polymers into the cells of a patient. Indeed, gene therapy has evolved immensely over the years. In 2016 for example, scientists made significant progress using gene therapy for increasing the resistance of uninfected cells to HIV/Aids and even “snipping out” infected cells.

Unfortunately, during gene therapy, it is often difficult to deliver therapeutic agents into the right cells. It is especially true with those agents which are DNA or RNA-based. In a bid to solve this problem researchers have, over the last decades, often added compounds such as cholesterol into nanoparticles to ease the carriage of therapeutic agents into cells.

Despite these efforts, the rapid development of these carriers is significantly hampered. Researchers are mandated to test the nanoparticles in cell culture before testing them in animals. This requirement slows down the whole research process and deters the efficiency of investigation to pinpoint suitable nanoparticles.

The good news is that a team of researchers recently developed a novel nanoparticle testing technique that promises to hasten the development of gene therapies. This new technology does this through entirely dispensing with the cell culture testing and subsequently allowing for the rapid screening of nanoparticles to carry therapeutic agents to specific organs of the body.

A combined team of researchers from the Massachusetts Institute of Technology, University of Florida, and Georgia Institute of Technology developed this new technology using minuscule strands of DNA (58 nucleotides long) as barcodes.

This could allow researchers to test hundreds of different nanoparticles in a few animals all at the same time. In fact, experts believe that the technique will only require three animals for each set of nanoparticles tested.

According to the lead author of the study, James Dahlman, one of the researchers’ objectives was to enhance their understanding of the most critical factors that affect nanoparticle delivery.

Mr. Dahlman who is an assistant professor at Georgia Tech and also one of the paper’s corresponding authors also noted that the new technique would also help improve researchers’ understanding of how disease factors affect gene therapy.

The testing process starts with the preparation of nanoparticles which begins with an insertion of a strand of DNA which is assigned a unique barcode to each variant of the nanoparticle. Researchers then insert the nanoparticles into mice after which they examine the organs of the rat for the presence of the unique DNA barcodes. This ultimately makes it possible for researchers to test many nanoparticles concurrently.

It is important to note that the single-strand DNA barcode sequences are roughly the same size as microRNA, siRNA, and antisense oligonucleotides. Those above are all subjects of research into their possible use in gene therapy.

However, it is not clearly known whether the larger gene-based therapeutics can use this technique. It represents an area of interest for additional research.

While researchers are interested in identifying nanoparticles that deliver the therapeutic agents, they are also interested in the identification of the nanoparticles that can selectively deliver agents to specific organs. For example, nanoparticles meant for a tumor should only go to the tumor while those meant for the liver should go to the liver only.

As a matter of fact, the study also included a test on selective nanoparticle distribution using 30 different particles distributed in 8 various tissues of an animal model. According to the results, some of the particles never gained entry into the tissues while others were taken up in multiple tissues.

The results of the study were also in concurrence with previous studies on nanoparticles that selectively enter the lungs and the liver. However, the study did not feature the use of nanoparticles in delivering effective therapeutics although there is an intention to do this shortly.

According to Mr. Dahlman, the researchers aim at making a thousand nanoparticles and evaluating them a few hundred at a time. It would greatly enhance the speed of screening nanoparticles for gene therapy.

Dahlman also acknowledged the complex nature of nanoparticles noting that for every biomaterial available, it is possible to make hundreds of different nanoparticles using various components. After screening, all the promising nanoparticles would undergo additional/more advanced screening to determine their actual ability in therapeutic delivery.

In addition to that, Mr. Dahlman noted that nucleic acid therapies could hold the key to treating a number of serious diseases. Furthermore, he expressed hope that in providing clarity on how the therapeutic agents affect cells and how they can selectively target specific body organs the research would contribute widely to the field (medical).

It is particularly great news for those suffering from some serious diseases including heart diseases, liver disease, and possibly even HIV/Aids.

Notwithstanding that the new technique promises a greater future for gene therapy, it is not without its challenges;

• Firstly, there is a huge possibility that nanoparticles may merge. Because of this, only those structures that maintain stability in aqueous environments are tested.
• Secondly, researchers may only use this technique to screen nontoxic nanoparticles.
• There is a possibility of inflammation as a consequence of the inserted DNA. Researchers must, therefore, control for this.

The original research for the study took place in the laboratories of Robert Langer and Daniel Anderson. Mr. Langer is a professor at the David H. Koch Institute at MIT while Mr. Anderson is a Samuel A. Goldsmith Professor of Applied Biology also at MIT.

The National Institutes of Health supported the research which was reported in early 2017 in the Journal Proceedings of the National Academy of Sciences. The research is also accessible online. Aside from Dahlman, Langer, and Anderson, other authors of the research include;

• Kevin Kauffman (MIT)
• Yiping Xing (MIT)
• Taylor Shaw (MIT)
• Faryal Mir (MIT)
• Chloe Dlott (MIT)
• Eric Wang (University of Florida)