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Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates.

ABSTRACT: Self-replicating gene drives that can spread deleterious alleles through animal populations have been promoted as a much needed but controversial 'silver bullet' for controlling invasive alien species. Homing-based drives comprise an endonuclease and a guide RNA (gRNA) that are replicated during meiosis via homologous recombination. However, their efficacy for controlling wild populations is threatened by inherent polymorphic resistance and the creation of resistance alleles via non-homologous end-joining (NHEJ)-mediated DNA repair. We used stochastic individual-based models to identify realistic gene-drive strategies capable of eradicating vertebrate pest populations (mice, rats and rabbits) on islands. One popular strategy, a sex-reversing drive that converts heterozygous females into sterile males, failed to spread and required the ongoing deployment of gene-drive carriers to achieve eradication. Under alternative strategies, multiplexed gRNAs could overcome inherent polymorphic resistance and were required for eradication success even when the probability of NHEJ was low. Strategies causing homozygotic embryonic non-viability or homozygotic female sterility produced high probabilities of eradication and were robust to NHEJ-mediated deletion of the DNA sequence between multiplexed endonuclease recognition sites. The latter two strategies also purged the gene drive when eradication failed, therefore posing lower long-term risk should animals escape beyond target islands. Multiplexing gRNAs will be necessary if this technology is to be useful for insular extirpation attempts; however, precise knowledge of homing rates will be required to design low-risk gene drives with high probabilities of eradication success.

SUBMITTER: Prowse TAA

PROVIDER: S-EPMC5563802 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates.

Prowse Thomas A A TAA Cassey Phillip P Ross Joshua V JV Pfitzner Chandran C Wittmann Talia A TA Thomas Paul P

Proceedings. Biological sciences 20170801 1860

Self-replicating gene drives that can spread deleterious alleles through animal populations have been promoted as a much needed but controversial 'silver bullet' for controlling invasive alien species. Homing-based drives comprise an endonuclease and a guide RNA (gRNA) that are replicated during meiosis via homologous recombination. However, their efficacy for controlling wild populations is threatened by inherent polymorphic resistance and the creation of resistance alleles via non-homologous e ...[more]

PMID: 28794219

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Project description:Introduction and importanceVulvar penetrating trauma is a rather uncommon occurrence (1). Firearm injuries caused by low-velocity gravitational bullets are a common cause of injuries in war-torn countries such as Somalia [2] (Campbell and Wilbert, 2022). These types of injuries are inflicted on by-standers by wayward bullets. No standard consensus on the appropriate management of vulvar penetrating trauma has been established (3). Here in, we report the successful management of an impacted bullet in the clitoris by a simple incision under local anesthesia. The principles of vulva and clitoris tired bullet trauma management are discussed. In our case, we thought it to be rare and interesting, considering its occurrence.Case presentationIn this report, a 24-year-old woman (gravida 2, para 2) suffered from a vulvar area penetrating bullet injury. Imaging revealed that the foreign body was confined to the clitoris, and no evidence of other parts of the body. Under local anesthesia, the bullet was accessed and removed from the clitoris by performing a minor incision. No complications were observed following the surgical removal of the bullet.Clinical discussionNon-obstetric vulva trauma is an extremely rare occurrence. Typically, the cause of non-obstetric vulvar trauma includes sports-related injuries, straddle injuries, and midline splitting injuries. To the best of our knowledge, this case is unique due to the bullet being retained in the clitoris. The treatment of the foreign body is mostly surgical removal. Under local anesthesia, this patient underwent complete surgical removal of the metallic foreign body. During surgical excision, care should be taken not to damage the urethra and other pelvic issues.ConclusionTo the best of our knowledge, this is the first wayward bullet (not intended for the patient) injury penetrating the vulvar area with a retained bullet in the clitoris. In our case, we thought it to be rare and interesting, considering its occurrence.

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Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates.

Publications

Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates.

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