GeneOnline’s Pick: Novel Biotechnologies that Made a Splash in 2021

The GeneOnline team has assembled all the novel biotechnologies in 2021 selected by the readers, including mRNA technology, gene editing, and cell therapy. Allow us to help you keep up with the up-to-date therapies, and we look forward to introducing you to more new biotechnologies coming up in 2022.

mRNA Vaccines Have Been Revolutionized Thanks to COVID-19

Take the COVID-19 vaccine, for instance; by generating the spike proteins that stimulate the ones on the COVID-19 virus, it can induce the human immune system to produce specific antibodies against the virus.

The use of liquid nanoparticles (LNPs) allows for the in vivo delivery of unstable structures such as a single mRNA strand. In other words, the mRNA vaccines nowadays no longer require cell culture procedures; with the characteristics of short half-life and single strand, the risk of altering human DNA decreases.

The Emergence of Novel RNA Technologies 

A handful of novel RNA technique-related research has been noticed and invested, such as self-amplifying RNA (saRNA) and endless RNA (eRNA). 

The unique structure of eRNA makes itself a potential therapeutic target. Since there are no starting and ending points on eRNA, it is unlikely to be attacked by the immune system, thus maintaining its stability and prolonging the effectiveness of the treatment. With the translation modularity feature, the application of eRNA is broad; it can generate all kinds of peptides, enzymes, and antibodies, both inside and outside of the cells. In addition, eRNA is unlikely to pass down to the next generation; thus, it can be developed as a low-risk gene-editing technology.

Laronde, the company that developed eRNA, has already raised $440 million in Series B financing to advance the development of its eRNA platform and planned to create 100 new RNA medicines over the next ten years.

CRISPR and RNA Gene Editing

Despite not being nominated for the Nobel prize, the CRISPR technology achievement has earned Feng Zhang of MIT several publications in various international journals. The research, published in Nature on 20th August 2021, proposed a new RNA-delivery technique, SEND (Selective Endogenous eNcapsidation for cellular Delivery). 

By covering mRNA with PEG10 protein and modifying with fusogen after tagging the detectable mRNA sequence on target mRNA, RNA is able to combine with the target gene more precisely. More importantly, PEF10 is a protein already existing in the human body, thus being unlikely to induce an immune reaction, and increasing the efficiency of RNA delivery. 

The other marvelous result of the research is the discovery of a unique protein called Cas13bt. It can be packaged into adeno-associated viruses (AAV) and sent into the human body with its tiny structure. Applying Cas13 protein into RNA editing not only can maintain the low off-target feature but also can act as a drug delivery tool.

Improved CasMINI Editing System  

A research team from Stanford University proposed an improved CasMINI editing system in September 2021. The amino acid sequence in CasMini is half the size of the Cas9 / Cas12a proteins used in the typical CRISPR system, allowing for more precise delivery into target cells.

Cas12f, the editing protein used for CasMINI, is extracted from the archaea, modified using computer prediction with biology engineering, and contains a green fluorescent protein (GFP) insert.

The research showed that the editing efficiency of Cas12f is similar to the proteins used by CRISPR. And since the single-guide RNA design has been modified, gene editing can be higher precision and low off-target.

With the advantage of small structure and high precision of editing, CasMINI, as well as Cas13b, can be installed into AAV; thus, CasMINI can be applied to develop mRNA vaccines or other RNA technologies.

RNA Editing vs. CRISPR

The other concern of CRISPR is the potential for off-target effects. While RNA editing does not avoid this phenomenon entirely, it is less likely to have a severe and permanent effect on the genes. 

Additionally, RNA editing can regulate gene expression dynamically. Gene therapy typically targets the tissues or organs, making it challenging to regulate single gene expression, and it faces the challenge of regulating the expression of a single gene. But with RNA editing, regulating the gene expression can be more flexible without worrying about gene over-expression or under-expression. 

However, there are some challenges that RNA editing is currently facing. With the trend of novel treatment having smaller structures, the RNA editing system also requires improvement. 

That being said, while we are amazed by how fascinating medical technology has evolved, we should also notice that there is room for editing protein technology to improve. 

iPSC therapy, from Discovery to Development

In CAR T-cell therapy, T lymphocytes are extracted from the patient, modified, and reinfused back into the same patient. The modification process is complicated and needs to be tailored to an individual’s needs, making mass production difficult.

With the ability to explore the cause and progression of the disease, iPSC therapy has the potential to cure those incurable diseases.

With the proliferation of iPSC and gene-editing technology, it is possible to design a standardized therapy that targets NK cells and macrophages for cancer and other severe diseases in the future. Additionally, iPSC can also be applied to the treatments for several irreversible neurological disorders. Alternatively, it can be cultured in vitro into a brain-like organ to mimic the brain structures of patients, making it easier and more precisely to characterize the early stage of the disease, thus increasing the rate of early diagnosis of frontotemporal lobar degeneration (FTLD).

Numerous biotech companies are focusing on new cell and gene therapies targeting cancer and various severe diseases in 2022; some have already announced their plans and collaboration during the 40th J.P. Morgan HealthCare Conference. We can anticipate more novel and marvelous biotechnologies being developed to meet unmet medical needs soon.

Author

Aurora Mau