The technology was developed through a collaboration between research groups from Cornell University in the United States, Tel Aviv University, and the Technion. The study was led by Prof. Chris  A. Alabi and Prof. Matthew P. DeLisa from Cornell, collaborating with Prof. Avi Schroder from the Technion and TAU’s Prof. Ben Maoz of the Fleischman Faculty of Engineering and the Sagol School of Neuroscience and Prof. Uri Ashery of the Wise Faculty of Life Sciences and the Sagol School of Neuroscience, together with Prof. Christopher Alabi of Cornell. The findings were published in the Proceedings of the National Academy of Sciences (PNAS).

A Temporary “Mask” for Antibodies

In the study, the researchers developed an innovative approach based on temporarily “masking” the antibody using a synthetic molecule called SL4. This masking alters the antibody’s chemical properties in a controlled manner, allowing it to be encapsulated in lipid nanoparticles (LNPs), similar to the technology used to develop mRNA vaccines against COVID-19. Once the nanoparticles enter the cell, the antibody is released and regains its original structure and activity.

According to the researchers, this represents a significant breakthrough because approximately 80% of the proteins involved in human disease are located inside cells, making them inaccessible to most antibody-based therapies. The ability to deliver active antibodies into the cell cytoplasm opens new possibilities for treating diseases that have long been considered inaccessible to drug-based interventions.

The study demonstrated that the masking process significantly improves the efficiency with which antibodies can be encapsulated within lipid nanoparticles. Whereas unmodified antibodies were incorporated into the nanoparticles with relatively low efficiency, the masked antibodies achieved substantially higher encapsulation rates while retaining their stability and their ability to recognize the molecular target associated with the disease.

Reaching Targets Inside the Cell

The researchers tested the technology using a series of therapeutic antibodies targeting key biological pathways involved in disease development. The antibodies successfully entered cells and altered important signaling pathways associated with various types of cancer and inflammatory diseases. Following treatment, the activity of these pathways was significantly reduced, indicating that the antibodies had reached their intended targets and remained active inside the cells.

One of the study’s most promising findings emerged from a research model of Parkinson’s disease. The researchers used an antibody targeting alpha-synuclein, a protein whose accumulation in the brain is one of the hallmarks features of the disease. Following delivery of the antibody via the nanoparticles, they observed a significant reduction in the pathological aggregates of the protein in nerve cells, a finding that suggests that the technology could pave the way for new treatments for neurodegenerative diseases.

Beyond the Brain

The technology was also evaluated in a model of acute inflammatory lung injury. The researchers found that delivering antibodies via the lipid nanoparticles reduced inflammatory markers and improved pathological features of lung tissue. These findings highlight the potential for developing targeted therapies for severe inflammatory conditions.

Prof. Ben Maoz said: “For many years, delivering antibodies into cells has been considered one of the greatest challenges in the field of biologic therapies. We have succeeded in developing a system that enables antibodies to cross the cellular barrier and reach targets that were previously beyond their reach. We believe this is an important step toward expanding the therapeutic toolbox of modern medicine and paving the way for more precise treatments for complex diseases that still lack adequate therapeutic solutions.”

Toward a New Generation of Biologic Therapies

The researchers emphasize that the technology is still at the preclinical stage. Nevertheless, they believe the platform could lay the foundation for a new generation of biologic therapies. If it successfully progresses through development and clinical trials, it could, for the first time, enable the widespread use of antibodies against intracellular targets,  a goal widely regarded in the pharmaceutical industry as the next frontier of personalized medicine.

A new study at the Department of Anatomy and Anthropology of Tel Aviv University, and published in Scientific Reports, offers an explanation for one of the striking differences between men and women: the evolutionary development of the modern human pelvis. By comparing Neandertal pelvises with those of modern humans, the researchers reached a surprising conclusion: the unusual structure of the pelvis may not be that of the Neandertal, as has been assumed for decades, but rather that of the modern human male. According to the researchers, the male pelvis evolved into a unique biomechanical shock absorbing mechanism that stores energy and makes long-distance walking more efficient.

Led by Professor Yoel Rak of the Department of Anatomy and Anthropology at Tel Aviv University, and conducted in collaboration with researchers from Spain, the Technion, Bar-Ilan University, and Ono Academic College, the study is based on a comparison of two nearly complete male Neandertal pelvises, one from Kebara Cave in Israel  and the other from the Sima de los Huesos site in Spain, with dozens of modern human pelvises. Surprisingly, despite their large size and robust construction, the Neandertal pelvises were found to resemble those of modern human females in most measurements and proportions rather than those of modern human males.

Rethinking the Neandertal Pelvis

For many years, the Neandertal pelvis has been regarded as an anatomically unusual structure requiring a functional explanation of its own. The new findings, however, require a new look at Neandertal pelvises. The ancestral configuration may have been retained in Neandertals and in modern human females, while the modern human male pelvis underwent substantial evolutionary modification, giving rise to a distinctive anatomical configuration.

The central finding of the study is that the hip joints of modern human males are positioned farther forward on the pelvic ring than those of both modern human females and male Neandertals. According to the researchers, this shift created a new mechanical system in which the anterior thigh muscles, attached to the front of the pelvis, function much like a spring, while body weight acts on the posterior part of the pelvis .

The Neanderthal pelvis

A Natural Spring in Every Step

Professor Rak explains that during every step of bipedal walking, the body's center of mass drops downward. This drop traumatizes  the joints and requires energy to raise the body again in preparation for the next step. According to the new model, the distinctive geometry of the male pelvis enables the thigh muscles to cushion the drop of the body's center of mass, store potential energy during the step, and then release that energy immediately afterward- effectively "springing" the body upward into the next step.

In this way, the pelvis functions as a natural shock-absorber and energy-return system. It may reduce energy expenditure, improve walking efficiency, and thereby provide a significant advantage during long-distance travel on foot. The change in the position of the hip joints also required additional structural adaptations, including the thickening of the pubic bone and deepening of the anterior portion of the pelvis to withstand the new mechanical loads.

Why Did Male and Female Pelvises Evolve Differently?

Modern human females, by contrast, could not adopt the full suite of these modifications. According to the researchers, the constraints imposed by childbirth require a relatively shallow pelvis and a sufficiently wide birth canal. As a result, the female pelvis remains closer to the ancestral configuration—the same general configuration found in male Neandertals.

Professor Ella Been of Ono Academic College, a co-author of the study, adds: “This study demonstrates that questions about human evolution are not confined to the distant past. Understanding the evolution of our walking mechanism can contribute to contemporary research in biomechanics, musculoskeletal medicine, rehabilitation, and injury prevention. The perspective provided by the Neandertals helps us better understand the modern human body.”

A reconstruction of the skeleton

The Evolutionary Innovation May Be Us

Professor Rak emphasizes that the findings of the study change the way we understand the evolution of the human pelvis. It is not the Neandertal pelvis that is the anomaly requiring explanation. Rather, it is the pelvis of the modern human male. The mechanism that evolved within the human male represents the evolutionary innovation.

The researchers note that the study presents a new biomechanical model that may explain a substantial part of the human pelvis’s sexual dimorphism, the anatomical differences between females and males. The research also demonstrates that even in human macroscopic anatomy, a field that might appear to have been thoroughly explored, there is still potential to uncover previously unrecognized structures, geometries, and mechanisms of biological significance.