Nature | seven biotechnology worthy of attention in 2022

1: Fully sequenced human genome

When Karen MIGA, a genomics researcher at the University of California Santa Cruz, and Adam phillippy of the National Human Genome Institute in Bethesda, Maryland, launched the telomere telomere (T2T) alliance in 2019, about one tenth of the human genome was still unknown. Now, this number has fallen to zero. In a preprint published last May, the alliance reported the first end-to-end sequence of the human genome, adding nearly 200million new base pairs to the widely used human common genome sequence called grch38, and wrote the last chapter of the human genome project.

Grch38, first released in 2013, has always been a valuable sequence tool, but due to the short reading, it is not enough to clearly map the highly repetitive genome sequence, including telomeres and centromeres that coordinate the distribution of newly replicated DNA during cell division.
Long reading sequencing technology was developed by Pacific Biosciences in Menlo Park, California and Oxford nanopore technologies (ont) in Oxford, England. These technologies can sequence tens of thousands or even hundreds of thousands of bases in a single reading. These tiny variations like fingerprints allow them to track different repeats and complete the sequencing of the remaining genome. The ont platform also captures many DNA modifications that regulate gene expression, and T2T can also map these 'epigenetic tags' on a genome-wide scale.

2: Analyze protein structure
Structure determines function. Significant experimental and computational advances in the past two years have brought researchers unprecedented speed and resolution to determine protein structure. Alphafold2 structure prediction algorithm developed by deepmind relies on "deep learning" strategy to extrapolate the shape of folded protein from its amino acid sequence. After winning a decisive victory in the key evaluation competition of protein structure prediction in 2020, computational biologists tested their structure prediction algorithm head-on. "For some of these structures, the prediction results are almost surprisingly good," said Janet Thornton, a senior scientist in hinxton, UK, and former director of the European Institute of bioinformatics.
Since its public release in July last year, alphafold2 has been applied to proteome to determine the structure of all proteins expressed in humans and 20 model organisms, as well as nearly 440000 proteins in Swiss prot database, greatly increasing the amount of protein quality available for high confidence modeling data. Alphafold algorithm also proved its ability to deal with multi chain protein complexes.
At the same time, the improvement of cryo EM is enabling researchers to solve even the most challenging proteins and complexes through experiments.

3: Quantum simulation
Quantum computers manage data in the form of quantum bits. Coupled with the quantum physical phenomenon known as entanglement, quantum bits can interact at long distances. Compared with the equal digits in classical computers, these qubits can significantly increase the computing power that can be achieved by assigning quantitative qubits.

4: Precise genome editing

CRISPR – cas9 technology, with all its genome editing capabilities, is more suitable for gene inactivation than repair. This is because although the cas9 enzyme is relatively accurate in targeting the genome sequence, the repair of the resulting double strand cleavage by cells is not accurate.
David Liu, a chemical biologist at the University of Cambridge, pointed out that most genetic diseases require genetic modification rather than destruction. Liu and his team have developed two promising ways to do this. Both take advantage of the precise targeting of CRISPR, which also limits the ability of cas9 to cut DNA at this site. The first, called base editing, couples the catalytically impaired form of cas9 to an enzyme that helps chemically convert one nucleotide to another - for example, cytosine to thymine or adenine to guanine. The new generation of prime editing can not only convert any base into other types of bases, but also accurately insert DNA sequences into the genome. Single base editing technology first appeared in scientific papers in 2016, and now the treatment under research based on this technology is about to enter the stage of clinical development.

5: Targeted gene therapy
Nucleic acid based drugs may have an impact in clinical practice, but they are still very limited in applicable tissues. Most treatments require local administration or in vitro operation of cells collected from patients and transplanted back into patients. One exception is the liver, an organ that filters blood, which is a major target for specific drug delivery. Intravenous infusion or even subcutaneous injection can achieve the effect of liver specific delivery.
Adeno-associated virus is the preferred vector for many gene therapies. Animal studies have shown that careful selection of the correct virus combined with tissue-specific gene promoters can achieve efficient, organ specific delivery.
Lipid nanoparticles provide a non viral alternative, and several studies published in the past few years have highlighted the potential to adjust their specificity. For example, the selective organ targeting (sort) method developed by Daniel siegwart, a biochemist at Southwestern Medical Center, and his colleagues can quickly generate and screen lipid nanoparticles.

6: Spatial multiomics
The explosive growth of the development of single-cell genomics means that researchers can now derive genetic, transcriptomic, epigenetic and proteomic insights from single cells at the same time. But single cell technology also sacrifices vital information to separate these cells from their native environment.
In 2016, researchers led by Joakim Lundeberg of KTH Royal Institute of technology in Stockholm devised a strategy to overcome this problem. The team prepared slides with bar coded oligonucleotides - short stranded RNA or DNA - to capture messenger RNA from complete tissue sections, so that each transcript can be assigned to a specific location in the sample according to its bar code. Lundeberg said, "no one really believes that we can pull out the whole transcriptome analysis from tissue sections." "But the result was surprisingly easy."
The field of space transcriptomics broke out later. There are now several commercial systems available, including the visium spatial gene expression platform from 10x genomics, which is based on Lundeberg's technology.

7: CRISPR based diagnosis
The ability of CRISPR – CAS system to accurately cut specific nucleic acid sequences stems from its role as a bacterial 'immune system' against viral infection. But not all CAS enzymes are equal. The characteristics of different CAS enzymes are different. Cas9 is mainly used for CRISPR based genome modification, while CRISPR based diagnostic testing mainly uses cas13 discovered by Dr. Zhang Feng's team in 2016. Under the guidance of RNA, cas13 can not only cut the target sequence, but also cut any surrounding RNA molecules.
RNA amplification procedures can improve the sensitivity to trace viral sequences. Sabeti and her colleagues developed a microfluidic system to screen multiple pathogens in parallel using genetic material amplified from only a few microliters of samples. "At present, we have a test method that can detect 21 viruses at the same time, and each sample is less than $10," she said Sabeti and her colleagues have developed CRISPR based tools to simultaneously detect more than 169 human viruses, she added.