Page - 102 - in Critical Issues in Science, Technology and Society Studies - Conference Proceedings of the 17th STS Conference Graz 2018

stop the spread. The other approach of Target Malaria is a CRISPR/Cas-based gene drive which is used to confer infertility in females. In the CRISPR/Cas-approach, a gene cassette containing the CRISPR/Cas gene and specific gRNAs as well as cargo genes that reduce female fertility are inserted into the mosquito’s genome. When mating with a wildtype female then all offspring will be homozygous gene drive carriers. After fertilization, CRISPR/Cas recognizes the complementary locus on the homologous wildtype chromosome and makes a cut. The cell’s DNA-repair mechanism recognizes that cut and in the best scenario, uses the gene drive containing chromosome as a repair template, thereby copying the gene drive cassette (as explained in [4] and successfully demonstrated in yeast in [11]). Thus, this technique allows to transform heterozygous carriers into homozygous gene drive carriers. One major genetic drawback consists in the fact that when a cut by CRISPR is not repaired by homology-directed repair, it not only impedes the copying of the gene drive cassette but also creates a homing resistant allele which will be passed on to offspring generations. Furthermore, there are serious indications of a problem with incomplete or imperfect copying into the target locus, as well as off-target effects due to lacking specificity of the system. Sequence polymorphisms and maternal effects also make organisms resistant to homing. However, the CRISPR/Cas9 system is relatively new and currently one of the most heavily researched technologies in biology, thus further improvements (e.g. regarding specificity) are to be expected and already, there are some viable strategies to overcome the most obvious issues [11], [12]. The ecological implications harbor all the general problems associated with gene drives. For instance, there is the issue of lowered fitness. A population eradication would reduce diversity. Resistance formation is a major problem in the ecosystem as well, as it would confer an inheritable fitness gain that would persist in the population’s gene pool and may lead to the failure of the gene drive. Furthermore, the CRISPR/Cas-based gene drives are thought to be highly invasive, wherein a small number of carrier-individuals could potentially cause the spread of the gene drive into neighboring populations [13]. Thus, confinement may be a problematic issue with this technique. This approach just as X-Shredder, may favor alternative vector species and trigger the coevolution of the pathogen [4], [14]. Beyond that, there is probably going to be transgenic contamination of an ecosystem, in so far as non-functioning gene drive components in the genome may persist in wild populations. Dengue – RIDL Another vector-transferred disease, which was already targeted by a SPAGE technique is dengue. This technique is called RIDL, which stands for Release of Insects Carrying a Dominant Lethal. This non-gene-drive technique comes in two varieties: the bi-sex RIDL and female specific RIDL. RIDL works using multiple mass releases of male GMO mosquitoes with GMOs to one wild type release ratios as high as 54:1 [15]. The GMOs carry a gene that will kill offspring during early life stages. The bi-sex RIDL kills offspring regardless of sex and is therefore self- limiting because after one generation all GMOs are dead. The female specific fsRIDL on the other hand only kills female offspring. Male offspring is then heterozygous for the lethal gene. In the next generation these males mate again with female wild types and half of their offspring will heterozygously inherit the deadly gene where again females will die. The other half of offspring 102