One of the fundamental factors contributing to the deterioration of kidney function prior to transplantation is the development of inflammation in stressed kidney tissue. Therapeutic strategies that inhibit inflammation are based, for example, on blocking the activity of pro-inflammatory cytokines TNFa and IL-6, which prolongs kidney activity in experimental animal models [doi:10.1038/s41598-021-02864-1]. In this regard, using the acquired aptamer platform, NanoSanguis will develop and test a proprietary biomolecular filter as an additional element of the extracorporeal kidney perfusion dialysis system, which will effectively and safely remove selected pro-inflammatory cytokines, e.g., TNFa and IL-6.

The design of the filter selectively capturing pro-inflammatory cytokines will include the development of previously identified aptamers (oligonucleotides) targeting cytokines (e.g., IL-6 and TNFa). Aptamers are a relatively new class of biological molecules for biomedical applications.

Aptamers obtained by the SELEX method using oligonucleotide libraries enriched with modified nucleotides are characterized by increased binding strength to specific molecular targets and increased stability required for medical devices. The production of aptamers that selectively capture selected cytokines will be possible thanks to technology developed on the basis of patents PL239946B1, EP3350195B1, and US10450673, which NanoGroup S.A. acquired as part of the transaction. The aptamers obtained so far and those identified in the course of R&D work will be optimized, produced on a semi-technical scale, immobilized on a biocompatible solid bed, and used to manufacture a filter. ‘s work will include biochemical functional tests, i.e., the efficiency of the process of capturing selected pro-inflammatory cytokines from the perfusion fluid will be determined.

In addition, thanks to the use of a filter device in the dialysis system that selectively captures selected pro-inflammatory cytokines, it will be possible to remove molecules that are not effectively removed during conventional hemodialysis and that play a key role in progressive kidney degradation. None of the dialysis products currently available on the market offer the possibility of selectively capturing a specific molecule. Thus, the innovation of the product planned for development will be characterized by a significant novelty in relation to available dialysis products.

The complementary action of the filter to the dialysis system developed as part of NanOX will increase the effectiveness of removing specific toxins that play a key role in the process of kidney tissue degradation.

The aptamers present in the filter bind and remove only specific molecular targets, leaving other components intact (without affecting their function).

As part of this activity, NanoGroup plans to continue the Pure Biologics/Doto Medical project in the future, which aims to develop an innovative medical device based on the developed aptamer technology. According to the adopted assumptions, the medical device under development (selective biomolecular filter) should significantly improve the effectiveness of removing toxins from the body during hemodialysis performed on patients suffering from, for example, chronic kidney disease (CKD).

The project has been divided into subprojects (A) and (B), each of which will develop an adsorber (filter) targeting different molecular targets. The effect of toxin capture by the adsorbent (A) will be to preserve residual kidney function, while the use of the adsorbent developed in project (B) will reduce the risk of cardiovascular disease and mortality in patients with CKD.

Problems arising in therapy using currently available drugs (rapid metabolism and excretion from the body, unfavorable biodistribution) are solved in two ways. One is to search for new therapeutic preparations, the other is to develop appropriate drug delivery systems.

Among drug carriers, oligonucleotide carriers – aptamers – deserve attention due to their low immunogenicity. The use of this type of conjugate can ensure better bioavailability and resistance to degradation, reduce the immunogenicity of the drug, ensure prolonged release of the therapeutic substance, leading to an extension of its duration of action, and in the case of chemotherapy, to the saturation of cancer cells with the drug, which leads to an increase in the effectiveness of the therapeutic process.

Currently, the development of aptamer technology, which are single-stranded oligonucleotides that bind with high affinity and high selectivity to selected molecular targets (biomarkers), may compete with ADCs (antibody drug conjugates). These compounds have enormous therapeutic potential, including in oncology, where aptamer-drug conjugates can be used to deliver tumor-destroying substances directly to cancer cells.

The use of aptamer technology may lead to the development of drugs with minimal side effects. This is due to their selective action at the molecular level and low molecular weight.

The result of the project will be a conjugate consisting of a carrier molecule linked to a cytostatic drug. What distinguishes the product being developed from other solutions of this type (e.g., antibody-drug conjugates) is the use of an aptamer—a single-stranded DNA molecule—as a carrier. The aptamer with the attached drug molecule will not only be highly selective for a specific type of cancer, but also (due to its size), unlike antibody-drug conjugates, will have high penetration of cancerous tissue. An innovative approach is the introduction of additional modifications to the aptamer molecule (using the aptamer platform developed by Pure Biologics for the selection of modified aptamers), which will increase the stability of the aptamer and, consequently, the entire conjugate.