Only one other company, Sangamo Therapeutics, has tried gene editing inside the body, to treat metabolic diseases using a tool called zinc fingers
The previous generation genome editor, called zinc fingers
, had no problem reaching DNA that's wrapped around nucleosomes, Carroll's team reported, according to STAT.
Klug, "The discovery of zinc fingers
and their development for practical applications in gene regulation and genome manipulation," Quarterly Reviews of Biophysics, vol.
The technology is based on a type of DNA-binding proteins known as zinc fingers
KLF6 is a protein belonging to the family of Kruppel factors or transcription KLFs type, this transcription factor is characterized by three DNA binding domains, called zinc fingers
. KLF6 has great importance in the control of various processes as cell growth, cell differentiation, apoptosis and angiogenesis (Gehrau et al., 2011; Lang et al., 2013).
In 1996, for the first time, it was shown that protein domains such as "zinc fingers
" coupled with Fokl endonuclease domains act as site-specific nucleases (zinc finger
nucleases (ZFNs)), which cleave the DNA in vitro in strictly defined regions .
Among the metalloproteins and metal-binding domains, the zinc finger
motif, characterized by the presence of a structural zinc ion, is surely the most emblematic [12-15] as it has been intensively studied for its known ubiquitous presence in the biological world (e.g., 3% of the genes of the human genome encode for zinc fingers
containing proteins [16, 17]).
The N-terminal region of the encoded peptide chain has a KRAB domain, whereas the C-terminal region has 14 [C.sub.2][H.sub.2] zinc fingers
; therefore, it is a typical KRAB/[C.sub.2][H.sub.2] zinc finger
An experimentally tested scenario for the structural evolution of eukaryotic Cys2His2 Zinc Fingers
from Eubacterial Ros Homologs.
To artificially confer this invulnerability, June's team removed T cells from 12 HIV-infected patients who were taking standard antiviral drugs and used zinc fingers
to delete the doorway receptor gene.
While they represented a great improvement over zinc fingers
, however, TALENs are large proteins that are cumbersome to work with and deliver into cells.
ZNF441 (gi308153532, UniProt: Q8N8Z8) is a nuclear protein with 693 amino acids which belongs to the Krueppel [C.sub.2][H.sub.2]-type zinc finger
protein family, and it contains 19 [C.sub.2][H.sub.2]-type zinc fingers
and 1 KRAB-domain (UniProt entry).