Scientists create ‘smart bomb’ drug to target leukemia in children

Researchers at the University of Southern California and the University of Illinois have invented a drug designed to attack the most common and deadly form of childhood cancer, B-lineage acute lymphoblastic leukemia.

The so-called “smart bomb” drug has the potential to save children who have relapsed after initial chemotherapy and otherwise face a 20 percent chance of long-term survival.  

The drug targets a defective gene that leads to the production of an abnormal form of the protein CD22. That abnormal gene is resistant to standard treatments for the leukemia— including chemotherapy, total-body irradiation and bone marrow transplantation.

Previous research by the study authors indicated that this polypeptide-based system effectively and safely knocked down targeted genes in animals, study author Fatih Uckun, professor of research pediatrics at USC and head of translational research in leukemia lymphoma at the Children’s Center for Cancer and Blood Diseases of Children’s Hospital Los Angeles, told

“Smart bomb” drugs work by directing defective cells to self-destruct by explosion or implosion without impacting surrounding cells.

Before engineering the mechanism to knock down the leukemia cells for the new study, researchers had to identify the abnormality that drove the growth of leukemia cells, Uckun said.

“The CD22 is a mutant product that is only made in leukemia cells, and we found that 97 percent—almost all of the leukemia in childhood— has this,” Uckun told “What this does is it drives leukemia cells to grow.”
                                                                                                                                                                                    CD22 is also common in strains of leukemia that affect adults. The gene is present in 100 percent of aggressive Burkitt’s leukemia and lymphoma, 98 percent of cell leukemia and lymphoma, and 80 percent of patients with other forms of B-lineage leukemia and lymphoma.

To create the mechanism that would target CD22, Uckun collaborated with Jianjun Cheng, associate professor of material science and engineering at the University of Illinois at Urbana-Champaign and an affiliate with the NCI Alliance for Nanotechnology in Cancer.

Cheng and his colleagues created synthetic fragments of genetic material— rationally designed, small interfering RNA— that bind to the message of CD22 and trigger its degradation inside the cell. The device delivered the RNA to the defective gene.

The “smart bomb” has a diameter of only 100 nanometers— making it one of a handful of nanomedicines that can treat disease at a molecular level, according to a news release.

From concept to publication of the current study, the research took about four years and three months, Uckun said.

Next, Uckun and his colleagues are exploring different packaging and delivery options for the RNA. They hope to answer questions like when to treat, how long to treat, what dose to use in treatments, what treatment schedules to use, and what form the treatment should assume.

“The major discovery was the driver lesion and how to knock it down, Uckun said. “Now the question is not if it will work, but how will we make it work best?”

The research was published in the Oct. 28 issue of the journal EBioMedicine.