SEND Delivery System for Gene Therapy

Researchers at MIT and Howard Hughes Medical Institute have developed a new way to deliver molecular therapies to cells. The system, called SEND, can be programmed to encapsulate and deliver different RNA cargoes.

SEND (Selective Endogenous eNcapsidation for cellular Delivery), "dazzles with its sheer ingenuity," notes Singuarity Hub. SEND "commandeers human proteins to make delivery vehicles that shuttle in new genetic elements. In a series of tests, the team embedded RNA cargo and CRISPR components inside cultured cells in a dish. The cells, acting as packing factories, used human proteins to encapsulate the genetic material, forming tiny balloon-like vessels that can be collected as a treatment."

"The biomedical community has been developing powerful molecular therapeutics, but delivering them to cells in a precise and efficient way is challenging," says senior researcher Feng Zhang, a CRISPR pioneer, in a press release issued by MIT. "SEND has the potential to overcome these challenges."

SEND takes advantage of molecules made by human cells. A paper published in Science describes how the researchers engineered a protein called PEG10, which exists naturally in humans, to selectively package and deliver RNA cargos. The researchers used SEND to deliver the CRISPR-Cas9 gene editing system to mouse and human cells to edit targeted genes.

Using SEND, the researchers delivered a CRISPR system that removes a cancer-causing gene in cells in a dish originally derived from brain cancer. "The system efficiently cut out roughly 60 percent of the gene in recipient cells," notes Singularity Hub. "But it only did so when SEND shuttled the CRISPR components into the cell, showing that SEND only delivers genetic material that’s been custom-made for its transport."

Since SEND is composed of proteins that are produced naturally in the body, it could open up opportunities to deliver gene therapies repeatedly without triggering adverse immune responses, and with minimal side effects.

"This study shows that there are probably other RNA transfer systems in the human body that can also be harnessed for therapeutic purposes,” says researcher Michael Segel. “It also raises some really fascinating questions about what the natural roles of these proteins might be."

The researchers plan to test SEND in animals and further engineer the system to deliver molecular therapies to a variety of living cell types.

"We're excited to keep pushing this approach forward," concludes Zhang. "The realization that we can use PEG10, and most likely other proteins, to engineer a delivery pathway in the human body to package and deliver new RNA and other potential therapies is a really powerful concept."