Synthetic biology is the design and construction of new biological parts, devices, and systems, and the re-design of existing, natural biological systems for useful purposes.
The functional aspects of this definition are rooted in molecular biology and biotechnology.
As the usage of the term has expanded, synthetic biology was recently defined as the artificial design and engineering of biological systems and living organisms for purposes of improving applications for industry or biological research.
In general, its purpose can be described as the design and construction of novel artificial biological pathways, organisms or devices, or the redesign of existing natural biological systems.
Synthetic biology has traditionally been divided into two different approaches. Top-down synthetic biology involves using metabolic and genetic engineering techniques to impart new functions to living cells. Bottom-up synthetic biology involves creating new biological systems in vitro by bringing together ‘non-living’ biomolecular components, often with the aim of constructing an artificial cell. Biological systems are thus assembled module-by-module. Cell-free protein expression systems are often employed, as are membrane-based molecular machinery. There are increasing efforts to bridge the divide between these approaches by forming hybrid living/synthetic cells, and engineering communication between the living and synthetic cell populations.
Genome editing is not a new concept to the scientific community and has been around for decades. However, directing precise sequence changes at desired sites has remained a difficult and tedious challenge for researchers. Limited successes have been achieved with oligonucleotides, small molecules, or self-splicing introns, but the development of site-directed zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) has facilitated sequence-specific manipulations. Nevertheless, difficulties of protein design, synthesis, and testing have slowed adoption of these engineered nucleases for routine use in genome editing experiments. The most recent gene-editing technology, the CRISPR-Cas9 system, largely overcomes these difficulties, making it an attractive method for genome editing. It is critical that we adopt a workflow and use technology that can make genome editing efficient by accurately identifying on- and off-target mutations, producing a gene-edited organism that may have fewer or no off-targeted gene side effects. Today, with the aid of gene-editing tools, researchers can quickly generate model organisms that can be used to study human diseases, test efficacy of various drugs, and even create genetically modified organisms during times of an epidemic, as has been done for the Aedes aegypti mosquito, a vector for the Zika virus.
Understanding the CRISPR-Cas9 gene editing system
Clustered regularly interspaced short palindromic repeats (CRISPRs) belong to a class of repeated DNA sequences that work together with CRISPR-associated (Cas) genes to protect bacteria and archaea from invading foreign nucleotides, such as those from phages and plasmid DNA. Upon injection of phage-DNA into the bacteria, the phage-DNA is cut into small pieces and incorporated into the CRISPR locus. This locus, now containing information about the foreign phage-DNA is transcribed, this CRISPR-RNA (crRNA) along with a second non-coding RNA, trans-activating CRISPR RNA (tracrRNA), then forms a ribonucleoprotein complex with the Cas9 endonuclease and cuts the foreign DNA from this specific phage. So, a bacteria carrying information about a specific phage-DNA can have immunity towards attack from that phage. In this way, bacteria and archaea have evolved an adaptive immune response against invading DNA and can protect themselves in the future when attacked by the same phage.
