Nature/SigTrans 2020: Therapeutic siRNA: state of the art

Hu et al., 2020 …”Seven siRNAs are undergoing phase 3 clinical studies, and more candidates are in the early developmental stage. Various delivery systems, e.g., LNPs, DPC™, TRiM™, GalNAc–siRNA conjugates, LODER™ polymers, exosomes and polypeptide nanoparticles (PNPs), have been explored”

RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients

Talia Golan, Elina Zorde Khvalevsky, Ayala Hubert, Rachel Malka Gabai, Naama Hen, Amiel Segal, Abraham Domb, Gil Harari, Eliel Ben David, Stephen Raskin, Yuri Goldes, Eran Goldin, Rami Eliakim, Maor Lahav, Yael Kopleman, Alain Dancour, Amotz Shemi and Eithan Galun, Oncotarget May 19, 2015 ABSTRACT PURPOSE: The miniature biodegradable implant siG12D-LODER™ was inserted into a tumor […]

Mutant KRAS is a druggable target for pancreatic cancer

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery […]

Multistep, effective drug distribution within solid tumors

Amotz Shemi, Elina Zorde Khvalevsky, Rachel Malka Gabai, Abraham Domb, Yechezkel Barenholz, Oncotarget , Sep 22, 2015 Abstract: The distribution of drugs within solid tumors presents a long-standing barrier for efficient cancer therapies. Tumors are highly resistant to diffusion, and the lack of blood and lymphatic flows suppresses convection. Prolonged, continuous intratumoral drug delivery from a miniature drug source offers an […]

Preclinical Safety Evaluation in Rats of a Polymeric Matrix Containing an siRNA Drug Used as a Local and Prolonged Delivery System for Pancreatic Cancer Therapy

Ramot Y, Rotkopf S, Gabai RM, Khvalevsky EZ, Muravnik S, Marzoli GA, Domb AJ, Shemi A, Nyska A. Abstract: Conventional chemotherapy treatments for pancreatic cancer are mainly palliative. RNA interference (RNAi)-based drugs present the potential for a new targeted treatment. LOcal Drug EluteR (LODERTM) is a novel biodegradable polymeric matrix that shields drugs against enzymatic […]

Ammonium and arsenic trioxide are potent facilitators of oligonucleotide function when delivered by gymnosis

Xiaowei Zhang, Daniela Castanotto, Xueli Liu, Amotz Shemi and Cy A. Stein, Nucleic Acids Research, 2018 1 Abstract: Oligonucleotide (ON) concentrations employed for therapeutic applications vary widely, but in general are high enough to raise significant concerns for off target effects and cellular toxicity. However, lowering ON concentrations reduces the chances of a therapeutic response, […]

Better Targeting, Delivery of RNAi Therapies

Richard A. Stein. Genetic Engineering & Biotechnology News. 2017. An advantage of the LODER platform is that it delivers RNAi locally, within the tumor, Circumventing systemic toxicity and the need for large systemically administered doses. “We have preclinical and clinical data showing that our treatment is safe,” asserts Dr. Shemi. “It affects the development of […]

The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market

Ricardo Titze-de-Almeida, Catherine David & Simoneide Souza Titze-de-Almeida. Pharmaceutical Research. 2017. “KRAS-LODER made KRAS a druggable anticancer target. New drugs also targeting this oncogene are now in test and may represent future competitors of KRAS-LODER. KRAS-LODER is the only RNAi-based drug that provides a sustained release of siRNA into the tumor region thanks to a well-known […]

Pancreas adenocarcinoma: novel therapeutics

Benjamin A. Krantz, Kenneth H. Yu, Eileen M. O’Reilly. Chinese Clinical Oncology. 2017. “Targeting RAS by inhibiting translation using small-interfering RNAs is a novel strategy to decrease RAS activity. siRNA against the G12D mutant RAS RNA by local prolonged delivery, KRAS-LODER (Local Drug EluteR), has demonstrated decreased growth of human pancreatic tumor cells in vivo and […]

Silenseed Phase II pancreatic cancer drug trial to begin

Israeli drug development company Silenseed is to begin a Phase II multicenter trial for its pancreatic cancer treatment. The study, which has been approved by the US Food and Drug Administration (FDA), will be held at several leading medical centers in the US with the participation of 80 patients. At the same time, the Modi’in […]