Our genetic instructions are invaluable: DNA not only determines who we are, but it can also be used in medicine for gene therapy. It's not all: looking at it from a structural and physical point of view, a team of biotechnologists and materials physicists has developed the so-called "DNA hydrogels", dei polimeri la cui struttura è fatta di acidi nucleici e al cui interno troviamo dell’acqua.

These can be used in various biomedical applications: in the formulation of drugs, in gene therapy and cell therapy approaches.

DNA as a biomaterial shows qualities such as biocompatibility and biodegradability, which today are fundamental requirements for the development of new technologies. Furthermore, DNA responds to various physical stimuli, such as changes in temperature or pH, but also chemical and this makes the DNA structure itself controllable. In pharmacology it is very important to control the release of a drug, ed è a questo proposito che gli Idrogel trovano la loro vocazione.

An example: my therapeutic target is the intestine, il cui pH è neutro. Un farmaco assunto per via orale dovrà necessariamente passare per lo stomaco, a notoriously acidic environment; therefore having hydrogels that dissolve only in the presence of a neutral pH would protect my drug until it reaches its goal, the intestine, e sarà solo a questo punto che l’ idrogel si dissolverà e rilascerà il farmaco.

Finally, genetic engineering, with the advent of CRISPR / CAS9 technology, offers new insights. This molecular machinery, of bacterial origin, consists of two parts: le guide CRISPR e la proteina CAS9. The guides serve as a mold for the CAS9, responsible for cutting and any correction of the target DNA. DNA is, then, become re-programmable and adjustable, redefining the potential of DNA hydrogels. About that, in Massachusetts, researchers from MIT, led by Dr. Collins, they exploited Cas12a, una versione ottimizzata della Cas9, per rendere gli idrogel ancora più malleabili. Their hydrogels are programmable for the release of enzymes, cellule e molecole in contesti speciali.

Just think of the increasingly emerging anti-tumor cell therapy, in which the cells of the immune system are engineered to recognize and kill the tumor itself.

Not always, But, queste riescono a raggiungere facilmente l’organo interessato.

CRISPR System Controlled Gels: MIT researchers have created intelligent material, called hydrogel, whose structure is made up of DNA strands. CRISPR-Cas12a protein cuts DNA strands by changing the shape of gels that can be controlled for the release of drugs and particles to ignite an electrical circuit.

Therefore, having a vehicle that releases cells only in the affected organ has its advantages and that is why Dr.. Collins and his team also tested hydrogels for the release of immune system cells, testing its vitality within the hydrogel and successfully simulating its release in vitro.

Subsequently, the group of scientists tested its potential also in diagnostics. They inserted the hydrogels into small chips made up of a microfluidic chamber connected to an electronic circuit. Quest’ultimo si spegnerà quando il sistema entrerà in contatto con il contenuto genetico e l’idrogel cambierà forma.

It has been tested, for example, for the Ebola virus and to detect the presence of the antibiotic-resistant Staphylococcus aureus bacterium. The perspective is, then, to develop "smart drugs", able to take action only when needed, e dei sistemi diagnostici che funzionino da sensori che si accendano o spengano in presenza di malattia.

References:

https://www.advancedsciencenews.com/dna-hydrogels-for-biomedical-applications/

https://www.nature.com/articles/d41586-019-02542-3

https://science.sciencemag.org/content/365/6455/780

J. At the, D. J. Mooney, Nat. Rev. Mater. 1, 16071 (2016).