The Historical Context of Genome Editing from the MSOE Center for Biomolecular Modeling 1950

The Historical Context of Genome Editing From the MSOE Center for BioMolecular Modeling 1950

46 Human Chromosomes Counted (1956) Watson and Crick model of double- stranded DNA proposed (1953)

1960 Philadelphia Chromosome (1960) Central Dogma of Molecular Biology (1950’s - 60’s) Genetic defect linked Genetic information ows from to cancer DNA to RNA to Protein

1970 Restriction Endonucleases (1970) Oncogenes rst reported in chickens (1970) First restriction enzyme reported by Wilcox and Smith Reciprocal Translocation of Bcr-Abl (1973) Translocation between chromosomes 9 and 22 shown to be associated with CML DNA cloning/Genetic Engineering (1970’s) Nucleosome Structure (1974) First description of a nucleosome as the repeating structural subunit of chromatin

Sanger DNA Sequencing (1977) Asilomar Conference on Fred Sanger describes method Recombinant DNA (1975) of sequencing DNA using Discussion of ethical issues related to DNA experiments dideoxy-nucleotide chain terminators 1980

FISH technology (1982) Polymerase Chain Reaction (1983) Fluorescent DNA Kary Mullis develops techniue to exponentially copy probes used to a particular DNA sequence visualize speci c sequences

1990 Zinc Finger Proteins (1993)

Multiple zinc nger domains reported CRISPR discovered (1993) in TFIIIA Near perfect palindromic repeats reported in salt-tolerant microbe.

Polydactyl Zinc Fingers (1998) Dolly the sheep cloned through nuclear transplant (1996) Zinc nger domains are modi ed to target dierent 2000 double-stranded DNA sequences CRISPR Sequences found to be common in 2000 other Microbes (2000) Gleevec (Imatinib)(2001)

First small molecular inhibitor of the Bcr-Abl oncoprotein Human Genome Sequenced (2003) An international research project to determine the nucleotide sequence of human genome. ENCODE (2004)

A “big science” eort to CRISPR repeats include foreign DNA (2005) identify all the functional elements of the human CRISPR sequences reported to contain foreign DNA…sug- gesting an adaptive immune system iPSCs - Induced Pluripotent Stem Cells (2006) Mature dierentiated cells reprogrammed to CRISPR is an Adaptive Immune System (2007) become stem cells

CRISPR protects microbes from recurring virus infection Researchers begin mapping the 3D structure CRISPR targets DNA (2008) of the chromosomes in the nucleus (2009) CRISPR system cuts DNA of foreign pathogens The genome is a knot-free fractal globule

2010

TALENS (2010) Targeting CCR5 in HIV-AIDS Patients Transcription Activator Like Eector Nuclease proteins with ZFNs (2013) (TALENs) used to target DNA sequences Clinical trials investigating the use of ZFNs to confer resistance to HIV in AIDS patients Charpentier and Doudna describe single-guide RNA (2012) Addgene distributes CRISPR reagents to Feng Zhang modi es 25,000 labs over next 3 years (2013) CRISPR to edit mammalian genomes (2013) CRISPR - Cas9 Structure and Function (2014)

The molecular structure of CRISPR Cas9 is reported by Jennifer Doudna’s group

CRISPR goes viral (2013 - )

Asilomar 2 on CRISPR-based genome editing (2015) 2020 Researchers convene meeting to discuss ethical issues related to genome engineering