Human Practices

Prof. Amir Onn, Head of the Institute of Pulmonology at Sheba Medical Center and an expert in pulmonary oncology, met with our team on several occasions to discuss our project and offer invaluable clinical insights. Drawing from his extensive experience treating lung cancer patients, he introduced us to the most common mutations observed in practice, how mutations evolve throughout disease progression, and the importance of tailoring treatment lines for each patient. His personalized medicine approach deepened our understanding of lung cancer biology and guided us in framing our therapeutic strategy. Additionally, Prof. Onn delivered an educational session on lung cancer management from the physician’s perspective, helping us align our work with real clinical needs.

Prof. Ido Wolf, Head of the Oncology Division at Tel Aviv Sourasky Medical Center, was introduced to our project and offered valuable guidance during its early stages. He helped us better understand the clinical landscape of oncology and directed us to key cancer databases and resources that supported our research. His input contributed to shaping our initial exploration of relevant cancer types and therapeutic opportunities.

To explore the feasibility of targeting brain tumors with antisense oligonucleotides (ASOs), we consulted with Prof. Stuart Grossman, a leading neuro-oncologist at the Johns Hopkins Kimmel Cancer Center. Prof. Grossman shared his experience from a Phase II clinical trial involving Aprinocarsen, an ASO targeting PKCα, which showed no clinical benefit when administered intravenously to patients with brain tumors. He highlighted the key challenge of blood-brain barrier (BBB) penetration and explained that current delivery routes, such as intrathecal injection have major limitations in effectively reaching widely distributed tumors like glioblastoma (GBM), without compromising BBB integrity.

Based on his input, we reassessed our approach. Since our project’s primary focus is on ASO design and optimization, rather than drug delivery systems, we concluded that it would be more impactful and responsible to target cancers with simpler and more accessible delivery requirements.

Prof. Itai Benhar, an expert in antibody engineering at Tel Aviv University, delivered a lecture to our team about his research on bispecific antibodies and antibody-drug conjugates. He provided critical guidance on the design of the antibody component in our therapeutic complex and shared the initial plasmid sequence we used as a basis for our construct. His expertise played a key role in shaping the molecular design of our targeting strategy.

Prof. Rina Rosin-Arbesfeld, a colorectal cancer expert at Tel Aviv University, met with our team to discuss potential applications of our ASO approach in colon cancer. She shared insights from her research on the Wnt signaling pathway, particularly the APC gene, and introduced us to relevant cell lines, reagents, and delivery methods used in her lab. Prof. Rosin-Arbesfeld also expressed interest in helping us test synthetic lethality partners of APC in her ongoing studies.

On September 4th, we met with Prof. Jack S. Cohen, an expert in pharmacology and antisense oligonucleotides. Prof. Cohen earned his doctorate at Cambridge University and held research and faculty positions at the NIH, Harvard Medical School, Georgetown University, and later in Israel at Sheba Medical Center, Hebrew University, and Ben-Gurion University. With over 200 publications and a long history working on antisense oligonucleotides, he shared with us his unique perspective on the discovery and development of ASOs.

Pharmacology doctor at Ha'Ivrit University, Jerusalem. former CEO of LifeWave and current head of Drug Development Department at Starget Pharma. Advised about Target search and provided Pharmacokinetic input.

We had the opportunity to meet Dr. Oren Bogin, former CEO of Immunorizon and an expert in protein chemistry and biologics development. With his extensive experience in drug discovery and biological therapeutics, Dr. Bogin provided valuable advice on the delivery challenges of ASO-based therapies and reviewed the various delivery technologies currently available in the market. He strongly encouraged us to pursue an antibody-conjugation strategy, which aligns with our modular platform approach, as it offers both targeted delivery and clinical relevance. His insights helped refine our delivery strategy and strengthened the rationale behind integrating an antibody into our therapeutic complex.

We had the privilege of consulting with Dr. Nofar Mor from Sheba Medical Center, who specializes in developing RNA-based therapies for ultra-rare diseases. Dr. Mor generously shared her expertise on antisense oligonucleotide (ASO) protocols, helping us refine our experimental design and better understand the practical aspects of RNA therapeutics. In addition to her clinical work, Dr. Mor is a co-author of the book Target Identification and Validation in Drug Discovery: Methods and Protocols [1], which provided us with valuable insights into modern approaches for drug discovery and validation. Her guidance significantly contributed to shaping our project’s therapeutic strategy and strengthened the translational relevance of our work.

We collaborated with SKIP Therapeutics, a biotech company developing RNA-based therapies using antisense oligonucleotides (ASOs). The SKIP team supported us with expert guidance on ASO design and experimental execution in mammalian cell lines. They provided detailed protocols and generously supplied us with a MALAT1-targeting ASO as a positive control and a scrambled ASO as a negative control. Their support significantly enhanced the reliability and robustness of our in vitro experiments.

As part of our entrepreneurship and technology exploration, we held discussions with Creative Biolabs, a leading biotech company specializing in Antibody-Oligonucleotide Conjugates (AOCs). AOCs represent an emerging platform that combines the precision of oligonucleotides with the targeted delivery capabilities of antibodies, creating a powerful tool for therapeutic applications.

During these conversations, we learned about the different strategies for AOC synthesis-including ion-interaction coupling, avidin–biotin bridges, direct conjugation to amino acids, and hybridization-based assembly. Each method has unique advantages and trade-offs in terms of stability, cost, and lysosomal release efficiency.

These insights helped us evaluate how AOCs could complement our ASO-based therapeutic platform, particularly in enhancing delivery, improving tissue specificity, and ensuring therapeutic stability in vivo. Importantly, we discussed their potential applications in oncology, from gene silencing and targeted ASO delivery to immune modulation and biomarker detection.

By engaging with industry experts such as Creative Biolabs, we not only gained a clearer understanding of the practical challenges and opportunities in bringing AOCs into the clinic, but also strengthened the entrepreneurial perspective of our project - bridging the gap between academic innovation and translational biotechnology.

As part of our Human Practices work, we interviewed Ellen Nemetz, a 64-year-old artist from Arizona, USA, who was diagnosed with stage IV lung cancer 1.5 years ago. Ellen is a never-smoker and carries the KRAS-Q61H mutation, a rare and challenging mutation for which treatment options remain limited.

Ellen first experienced Bamberger–Marie syndrome, a rare condition affecting about 5% of lung cancer patients, causing swelling and pain in the legs. Initially, her doctors investigated her heart, liver, and kidneys, all of which appeared normal. When she also mentioned a persistent dry cough, imaging revealed a primary carcinoma.

Initially staged as 3B, a subsequent PET scan revealed a metastasis in her hip, upgrading the diagnosis to stage IV. At that time, the disease had not yet spread to her brain or major organs.

Ellen began treatment with a combination of cisplatin, Pemetrexed, and Keytruda (immunotherapy).

Ellen shared that cisplatin (chemotherapy) was the most difficult chemotherapy, with side effects sometimes compounded by anti-nausea medications. Constipation and fatigue were especially challenging. She emphasized the importance of staying active - returning to the gym helped her both physically and mentally.

Ellen emphasized the need for new treatments that address rare mutations like KRAS-Q61H, as current options remain limited.

She hopes future research will consider patients’ quality of life, provide clear communication about risks and benefits, and make innovative therapies accessible for rare mutation carriers.

Ellen Nemetz, provided explicit written consent to be identified by name and to include limited details above. All other participants remain anonymous.

We also interviewed a lung cancer patient who preferred to remain anonymous (“S”). She was diagnosed two and a half years ago after months of unexplained symptoms and multiple hospitalizations. The diagnosis came abruptly and insensitively, following an MRI that revealed a large stage IV lung tumor.

Initially, S responded remarkably well to a targeted therapy (dacomitinib), with tumors shrinking by more than 60% within days. However, after a year the disease progressed, with new metastases and multiple biopsies required to confirm recurrence. Because her tumor carried an EGFR mutation that is often resistant to immunotherapy, she faced difficult treatment decisions. Although offered a place in an early-stage clinical trial, she declined due to the uncertainty and instead began chemotherapy. She described this as “a completely different world”: compared to targeted therapy, chemotherapy brought severe fatigue, cognitive fog, and daily functional limitations.

Despite these challenges, S has managed to continue working part-time and relies heavily on supportive activities such as water exercise to maintain her well-being. She emphasized the heavy bureaucratic and financial burden of treatment, including prolonged struggles with insurance coverage and drug access. At times she felt that the responsibility for coordinating her care fell primarily on her and her sister, rather than the health system.

Her message to researchers developing new therapies was clear: beyond efficacy, it is critical to reduce toxicity, simplify access, and design solutions that are realistic for patients managing complex, long-term disease.

We interviewed clinicians, industry scientists, pharmacologists, and patients. All participants gave informed consent; we collected no identifiable medical data. Notes were anonymized and double-checked by two team members to reduce bias. We follow iGEM’s No Human Experimentation and Human Subjects Research policies.