PASTE is a three-part CRISPR tool invented at the MIT McGovern Institute for Brain Research. It’s composed of a modified CRISPR-Cas9 (it’s called nickase because it nicks a single DNA strand instead of cutting both) and two effectors: RT stands for reverse transcriptase (just like in prime editing) while LSR means large serine recombinase.
This brand-new molecular machine writes the genome in three steps. Step 1: the nickase finds the desired site. Step 2: the reverse transcriptase inserts a landing pad. Step 3: the recombinase lands there and delivers its large DNA cargo. The aim is to replace whole genes, when fixing mutations is not enough (one example is cystic fibrosis). Here are the links to learn more:
I must say that I’m a bit envious and eager to taste this kind of Brassica juncea with the “mustard bomb” mechanism prevented by knocking-out multiple copies of the gene responsible for the bitter taste.
From the base-editing idea first sketched out via email in 2013, to the invention of prime-editing in 2019. From the progeria mutation fixed in mice in 2021 to the upcoming clinical trial for coronary heart disease. The updated story of the most advanced CRISPR tools told by Harvard’s David Liu is not to be missed (here’s the link to the Life Itself conference organized by CNN).
The first Investigational New Drug (IND) application for base-editing technology has been cleared by the Food and Drug Administration. BEAM-101, developed by Beam Therapeutics, is an ex vivo base-editing product candidate, meaning that it uses a modified form of CRISPR capable of making single base changes without double-stranded DNA cleavage.
Here you can read a selection of notable comments about the landmark paper on in vivo genome-editing published in the New England Journal of Medicineon 26 June. The trial, conducted in the UK and New Zealand, produced the first-ever clinical data supporting the safety and efficacy of intravenous infusion of a single-dose CRISPR treatment. The treatment, developed by two US-based companies (Intellia Therapeutics and Regeneron Pharmaceuticals) targets a rare and fatal condition called transthyretin amyloidosis.
Jennifer Doudna (CRISPR co-inventor and co-founder of Intellia): “It’s a critical first step in being able to inactivate, repair, or replace any gene that causes disease, anywhere in the body” (source Science).
A paper published in Nature by CRISPR innovator David Liu and a giant in medical genetics, Francis Collins, raises great hopes for treating a rare, devastating pediatric disease causing premature-aging (Hutchinson-Gilford progeria syndrome). “The outcome is incredible,” according to gene-therapy researcher Guangping Gao. “Dance on the lab bench” amazing, according to editing pioneer Fyodor Urnov. Let’s be clear: the CRISPR variant called a base-editor has helped only progeria mice so far, but results are beyond anyone’s wildest expectations. One injection is enough to fix the single-letter mutation in several tissues, doubling mice’s lifespan. To learn more, see David Liu’s tweets and the NIH Director’s Blog.
European scientists must wait for the EC to carry out targeted consultations with Member States and EU-level stakeholders. Then the Commission study on new genomic techniques will be delivered by 30 April 2021. In the meantime, the United States has decided to relax the rules for biotech crops.
Do you remember prime editing? It’s the new ‘search-and-replace’ genome editing technology that mediates targeted insertions, deletions, all 12 possible base-to-base conversions, and combinations thereof. The first good news is that David Liu et al. adapted prime editors for use in rice and wheat, so don’t miss their paper in Nature Biotechnology.