ILRI’s gene-editing scientists closing in on vaccine against pig pandemic
The viral disease has a case fatality rate of 100 percent in pigs within six to 13 days of infection. A recent ASF outbreak took a quarter of the world’s pigs off the market, caused pork prices to spike, and pushed food inflation to an eight-year high, thereby hurting livelihoods.
In sub-Saharan Africa where the disease is present in over 26 countries, the negative consequences are particularly significant on smallholder farms, substantially impacting food security, incomes, and development.
Healthy pigs are infected when they come into contact with infected ones, and consume contaminated feed such as kitchen waste, food residues, and meat products. Infection can also result from contact with contaminated material such as farm equipment, vehicles, clothes and shoes, manure and urine, and bites by infectious ticks.
Warthogs and other wild pigs in Africa and wild boars in Europe and Asia are all susceptible to ASF infection. Currently, there is no treatment or vaccine to combat this devastating disease.
“The lack of safe and effective vaccines is the missing link in preventing and controlling the African swine fever,” says Dr. Hussein Abkallo, a biotechnologist at the International Livestock Research Institute (ILRI) in Nairobi.
The CRISPR/Cas9 technology borrows from an adaptive immune system naturally used by bacteria to defend themselves against re-infection by viruses. Bacteria defend themselves from viral re-invasion by using this system as a guided “molecular scissor” to recognise invading viruses and destroy them by precisely chopping up the viral DNA.
Biotechnologists borrowed this natural bacterial virus-fighting mechanism to design a tool that can precisely edit – add, delete, replace
– sections of organisms’ DNA, similar to how one would type/cut/paste words on a computer, in both basic and applied research.
The CRISPR/Cas9 system is able to precisely alter an organism’s DNA as it is flexible and efficiency makes it an easily programmable system that can read any DNA sequence of interest in a cell.
This programmed CRISPR/Cas 9 system can find a specific location in the genome and snip the DNA, creating a break.
The organism’s cell, sensing the break, naturally repairs by gluing the loose ends back together either by adding or deleting nucleotides, the basic building blocks of DNA.
This, in effect, induces the desired changes, such as disabling harmful bacteria’s genes responsible for severe diseases in humans or livestock, reducing their disease-causing effect.
Conventional genetic technologies for generating live-attenuated vaccines and attenuation by cell passage (where viruses are continuously grown in culture until they undergo genetic changes and subsequently weaken) are cumbersome and timeconsuming. It takes up to one year to develop a few vaccine candidates for African swine fever.
The CRISPR/Cas9 technology bypasses these challenges by allowing biotechnologists to modify or delete genes with precision and speed, thereby fast-tracking the development of multiple live-attenuated vaccines candidates.
Using this system, the scientists at ILRI say they have significantly reduced the time to generate African swine fever vaccine candidates to less than two months instead of the conventional genetic techniques, which take six months on average.
“Our gene-editing platform has enabled us to generate over 10 live-attenuated vaccine candidates within a shorter time.
Preliminary safety and efficacy results from some of the tested candidates are promising,” Dr. Abkallo notes.
Scientists have developed strategies to minimize the off-target effects in CRISPR-Cas9-mediated genome editing and put in place elaborate quality control measures to ensure that target genes are edited as desired.
They estimate that an ASF vaccine could benefit 6-17 million smallholder farmers keeping some 34 million pigs in sub-Saharan Africa.
That is if the current policy challenges policy and communication challenges to the adoption of gene editing are addressed. “The challenges with CRISPR/ Cas9 gene editing are more policy and communication-oriented than technical.
One of the main challenges has been the slow development of frameworks for regulating gene editing. In Kenya for instance, the National Biosafety Authority (NBA) has recently published local guidelines for regulating and adopting gene-editing applications and products in the region to unlock the limitless potential of the technology.
The new policy guidelines outline case-by-case scenarios spelling out the scope of regulations- what needs to be regulated under the biosafety law, and will not be regulated under the biosafety law.
In a nutshell, gene editing approaches for making genetic changes that are often indistinguishable from natural mutations are not considered a genetically modified organism (GMO).” says Dr. Abkallo. In developing such policies, it is worth noting that there is a need for clear and case-by-case guidelines and policies governing gene editing,” says Dr Abkallo.
The scientists are also concerned about the skepticism and misinformation around gene editing partly due to a lack of comprehensive understanding of the technology. “We need vibrant advocacy and coherent communication about the immense potential that gene editing holds in national and global growth and development.
To realize the benefits of gene-editing, there should be a dialogue between stakeholders researchers, policymakers, the public, and the regulators – to come up with a consensus for creating an enabling environment for the adoption of technology and the acceptance of gene-edited products.
Gene editing is already in use in multiple facets in agriculture, veterinary and human medicine, and the sooner we embrace it, the better,” he says. The CRISPR/Cas9 technique is already being used to improve agriculturally important crop traits, such as nutritional value, disease resistance, and herbicide tolerance.
A tomato with higher nutritional content was the first CRISPR-edited food to go on sale in the world. In medicine, CRISPR is revolutionizing experimental therapies for genetic disorders ranging from sickle cell disease to blindness, potentially helping transform the lives of patients with previously limited treatment options.
Several CGIAR centres are embracing the CRISPR/Cas9 technology in their genetic improvement mandate for a food and income secure future.
It is anticipated that gene editing will in fure help develop superior crops that can endure the vagaries of climate change, increase yield and enhance nutritional benefits hence supporting global food security for the ever-expanding human and livestock population, and lower environmental impact posed by agricultural practices.