CRISPR


A 'community town hall type meeting' was held on September 17th, 2017 in the St David Lecture, University of Otago to discuss daisy drive technology. The meeting was chaired by Professor Gemmell who leads the Trojan female technique for NZ pest control.

Kevin Esvelt

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Kevin Esvelt

Kevin presented a talk which illustrated the technology of daisy chain drive in lay terms and invited the public to become involved and to share their suggestions, concerns, and criticisms. How should this technology be tested for safety and stability? Where should field tests take place and how should they be monitored?

This open and community-responsive development approach is planned to be the polar opposite of the traditional closed-door strategy used for engineered crops. He left the audience with the following points to consider as pros and cons.

Daisy drive: reasons in favour
- humane: no poisons required
- local and species-specific
- open, community-guided research
- already committed to removing invasive rodents
- success would ultimately eliminate engineered genes
- development doesn’t mean agreeing to deployment

 Daisy drive: reasons against
- mostly theoretical
- unclear how to test spread and stability in the lab
- hard to predict outcomes of ecological change
- genetic control may have international complications
- some object to genome engineering
- may conflict with Maori values or be unsuitable for other reasons

Kevin emphasized the high risks that  New Zealand might face from the international community who may impose non-tariff trade barriers or from individuals who might seek to illegally introduce genetically modified animals into their own country. He cited the example of the illegal introduction of rabbit calicivirus from Australia to New Zealand in 1997.

For further information, see the Responsive Science website for New Zealand predator-free.

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The Department of Conservation has set a target for New Zealand to become pest free by 2050. This includes mice, rats, stoats, rabbits and possums. This is very unlikely to be achieved using the conventional methods of poisons, diseases, traps, shooting or other such methods. 

Previous posts have described the use of genetic drives to control pest populations (Trojan Female Technique) and CRISPR global gene drives

However, as Kevin Esvelt explains:  "the problem with current CRISPR-based gene drive systems is that they can spread indefinitely. That means releasing a handful of organisms could eventually affect every population of the target species throughout the world. It's unclear how these systems can be safely tested.

Standard drive systems spread indefinitely because a single piece of DNA encodes the desired alteration, the CRISPR system, and instructions to cut the original DNA sequence. In cells that produce sperm or eggs, CRISPR cuts the original version, causing the drive construct to be copied in its place. All of the organism's offspring will inherit a copy, editing will happen again in the offspring, and the process repeats until the drive system has spread through most or all of the population.

In daisy-chain drive systems, the CRISPR components are split up and scattered throughout the genome so that none of them can be copied on its own. Though physically separated, they're functionally arranged in a linear daisy-chain: element C causes element B to drive, and element B causes element A to drive.

Element C doesn't drive, so its abundance is limited by the number of daisy drive organisms released.  Natural selection will gradually eliminate C from the population. That means B will initially increase in abundance, then decline and vanish. In turn, A will increase even more rapidly, but eventually will run out of B and disappear -- as explained in the video above."

For more on Daisyfield Gene Drive Systems

A Community Meeting to discuss Daisy Drive Technology is being held in Dunedin, New Zealand on September 17th, 2017 at which Kevin Esvelt is the keynote speaker. More about this event after the 17th.

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Developments around CRISPR have made it possible to tackle some interesting practical problems such as making NZ pest-free by using gene drive.

What is CRISPR? Watch the TED Talk below.

What is gene drive? An explanation of CRISPR and gene drive have been previously posted. It is a natural system used by bacteria to protect themselves against viruses and is now being used routinely in genetics as a tool in research.

Recently the Department of Conservation has set a target for New Zealand to become pest free by 2050. This includes mice, rats, stoats, rabbits and possums. This is very unlikely to be achieved using the conventional methods of poisons, diseases, traps, shooting or other such methods as pointed out by Professor John Knight in the article in the ODT 10/10/2016.

Gene drive is our best hope or worst fear? Part of the fear comes from the unknown.  What is required is a very extensive public education effort to explain to people what gene drive is, how CRISPR works and what are the ethical issues. For pest control the objective would be to produce only male offsprings and thereby control the population.

Being an island  nation, we are ideally situated to use this method — we have been bold with innovation before — here is our chance again.

For an update on this issue, see: daisy-chain-gene drive for pest free nz

Jennifer Doudna - co-inventor of the CRISPR technology talks about the need for 'ethics of CRISPR'.

Following on the issues raised in a previous post, Jennifer and numerous colleagues have called for an international meeting to discuss the safe use of CRISPR and the ethics of being able to create "engineer humans" as well as other genetically modified organisms (GMO's)

It is important that all stake holders (excuse the jargon), which includes you and me, understand the potential and risks of this technology and to have an informed discussion in accordance with the principles of a pluralist democracy. For more , click here.

For an elegant explanation of the CRISPR-Cas9 system watch the video.

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CRISPR is causing a major upheaval in biomedical research.  It is cheap, quick and easy to use, and it has swept through labs around the world as a result.

What is CRISPR? - it is an abbreviation for ‘clustered regularly interspaced short palindromic repeats’. It was  initially found in bacteria as a resistance mechanism to foreign genetic material such as plasmids and phages.

CRISPRs are associated with cas genes that code for proteins related to CRISPRs —  Cas9 for instance  By delivering the Cas9 protein and appropriate guide RNAs into a cell, the organism's genome can be cut at any desired location. Researchers only need to order the RNA fragment; the other components can be bought off the shelf. Total cost: is as little as $30. This effectively democratises the technology so that anyone can use it.

Last year, bioengineer Daniel Anderson of the Massachusetts Institute of Technology in Cambridge and his colleagues used CRISPR in mice to correct a mutation associated with a human metabolic disease called tyrosinaemia. It was the first use of CRISPR to fix a disease-causing mutation in an adult animal — and an important step towards using the technology for gene therapy in humans.

What are the risks?

Many researchers are deeply worried that altering an entire population, or eliminating it altogether, could have drastic and unknown consequences for an ecosystem. They are also mindful that a guide RNA could mutate over time such that it targets a different part of the genome. This mutation could then race through the population, with unpredictable effects - the risk of the accidental release of an experimental gene-drive.

What is a gene-drive?

First let us look at how mutations are normally spread within  populations.

STD-1

With gene-drive the genetic change would spread rapidly throughout the population since at each mating the genetic change would occur in both parents.

GDI-1

For further information, the source article is: Nature 522, 20–24 (04 June 2015)