Ernesto Guccione, PhD, Associate Professor of Oncological Sciences and Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, focuses on altering gene expression within cells through the emerging science of splicing-modulating RNA therapeutics. His laboratory uses short fragments of chemically modified nucleic acids known as Splice-Switching Antisense Oligonucleotides (SSOs), which pair up with messenger RNA (mRNA) to alter their function. Splicing modulation allows Dr. Guccione to rearrange the different blocks of RNA so defective RNA can be replaced with healthy versions that are able to produce functional proteins to fight cancer or fix genetic diseases.

“Unlike gene therapy, which substitutes defective DNA, our approach essentially modulates RNA to make a different protein,” says Dr. Guccione. “We’re doing this with SSO technology, which provides for a sequence of steps that force the cell to cut and paste mRNAs and repair the disease-linked mutation.”

Dr. Guccione and his research team have been heartened by the recent U.S. Food and Drug Administration approval of several drugs that use gene splicing to correct genetic errors that interfere with the production of key proteins. One of those agents, Spinraza® from Biogen Inc., is a short string of synthetic material injected into the cerebrospinal fluid of people with spinal muscular atrophy who have a mutated or deleted survival motor neuron 1 (SMN1) gene. This breakthrough drug has achieved remarkable success in generating the deficient SMN protein, which is essential for motor neurons to function.

“With the success of Spinraza and other agents that will surely follow, we believe we’re in a unique and exciting place to bring SSO technology to fruition for patients with liver cancer, as well as neurological and metabolic diseases, who currently have limited therapeutic options,” says Dr. Guccione. To that end, he is building a team that combines the resources of his Mount Sinai lab and those of a partner in Singapore with human geneticists and venture capital firms to further develop the SSO platform.