Programmable Proteins in Synthetic Biology

Dear Colleagues,

Programmable proteins to detect, visualize, modulate, or eliminate proteins of choice in vitro and in vivo are essential to study the targets recognized and the biology that follows. The specificities of programmable proteins can be easily altered by designing their sequences and structures. The flexibility and modularity of these proteins are currently pivotal for synthetic biology and various medical applications.

For example, Zinc-fnger nuecleases (ZFNs) and transcription activator-like effector nucleases (TALENs) were initially invented as programmable gene-editing tools.  Subsequently, RNA-guided CRISPR/Cas endonucleases and relevant base editors have been extensively used for different uses based on recognizing specific nucleic acid sequences. By fusing the CRISPR/Cas module to transcriptional regulators, CRISPRi and CRISPRa were developed to control gene expression. More recently, CRISPR-based diagnostic tools are devised for rapid detection of viral sequences such as SARS-CoV-2.

The second example is the immunoglobulin-derived programmable proteins that bind to other molecules.  Recombinant antibodies including nanobodies (VHH) and bispecific antibodies show the binding specificity required for specific recognition of molecules of interest. By fusing to other proteins, nanobodies can detect their binding partners in vitro and in vivo. Reminiscent of antibodies, artificial scaffolds such as FingR and DARPin are also promising candidates for constructing novel binders.

In this Special issue, authors are invited to publish original research articles and reviews on various aspects of such programmable proteins.

Dr. Masahito Yamagata
Guest Editor

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