CRISPR and Genetic Engineering in Zoology: Novel Approaches for Wildlife Conservation and Ecological Restoration

Authors

  • Swati Soren
  • Kimaya Sethi
  • Vijay Kumar
  • Darshan Ambiga
  • Iram Fatima
  • Jagjeet Singh
  • Ankita Singh
  • Narotam Sharma
  • Ajay Singh

DOI:

https://doi.org/10.53555/jaz.v47i1.5348

Keywords:

CRISPR-Cas9, Genetic Rescue, Gene Drive, Wildlife Conservation, De-extinction, Ecological Restoration

Abstract

The Sixth Mass Extinction represents a profound biological crisis characterized by accelerated vertebrate population declines and the pervasive erosion of genetic diversity. Traditional conservation strategies, while essential, often fail to mitigate the mutational meltdown and loss of adaptive plasticity inherent in fragmented populations. This review examines the transformative shift in zoology from passive preservation to active genetic intervention facilitated by CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology. We provide a comprehensive analysis of the molecular toolkit spanning traditional CRISPR-Cas9 to high precision base and prime editing and its diverse applications in wildlife conservation. Key themes include genetic rescue through the introduction of rare alleles, as exemplified by the Florida panther, and assisted evolution in climate vulnerable taxa such as scleractinian corals. Furthermore, we explore the potent role of RNA guided gene drives in eradicating invasive species and suppressing disease vectors, alongside the provocative science of de-extinction aimed at restoring ecological functions via proxy species like the woolly mammoth. A critical focus is placed on the technical and biological hurdles of evolutionary resistance, which threatens the long-term efficacy of these interventions. Finally, we synthesize the ethical, legal, and social frameworks necessary to navigate the wicked problems of synthetic biology. We conclude that while CRISPR offers an unprecedented lifeline for biodiversity, its success depends on the integration of rigorous ecological modelling, transboundary governance, and a commitment to procedural environmental justice.

Downloads

Download data is not yet available.

Author Biographies

Swati Soren

Department of Zoology, Jamshedpur Co-Operative College, Jamshedpur, Jharkhand, India

Kimaya Sethi

Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, Kerala, India

Vijay Kumar

Saini Clinical Path Laboratory, Saini Heart Care Centre, Fatehabad, Haryana, India

Darshan Ambiga

CRIS DNA Labs - Centre for Research and Innovative Scientific Studies, East Hope Town, Dehradun, Uttarakhand, India

Iram Fatima

Department of Zoology, Netaji Subhas University, Jamshedpur, Jharkhand, India

Jagjeet Singh

CRIS DNA Labs - Centre for Research and Innovative Scientific Studies, East Hope Town, Dehradun, Uttarakhand, India

Ankita Singh

Uttaranchal Institute of Technology, Uttaranchal University, Dehradun, Uttarakhand, India

Narotam Sharma

Department of Chemistry, Uttaranchal Institute of Technology, Uttaranchal University, Dehradun, Uttarakhand, India

Ajay Singh

School of Applied and Life Sciences (SALS), Uttaranchal University, Dehradun, Uttarakhand, India

References

1. Ceballos G, Ehrlich PR, Dirzo R. Biological annihilation via the ongoing sixth mass extinction signaled by vertebrate population losses and declines. Proc Natl Acad Sci U S A. 2017;114(30):E6089-E6096.

2. Doudna JA, Charpentier E. Genome editing: the new frontier of genome engineering with CRISPR-Cas9. Science. 2014;346(6213):1258096.

3. Pimm SL, Jenkins CN, Abell R, Brooks TM, Gittleman JL, Joppa LN, Raven PH, Roberts CM, Sexton JO. The biodiversity of species and their rates of extinction, distribution, and protection. Science. 2014;344(6187):1246752.

4. Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016;533(7603):420-424.

5. Gaudelli NM, Komor AC, Rees HA, Packer MS, Badran AH, Bryson DI, Liu DR. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature. 2017; 551(7681):464-471.

6. Anzalone AV, Randolph PB, Davis JR, Sousa AA, Koblan LW, Levy JM, Chen PJ, Wilson C, Newby GA, Raguram A, Liu DR. Prime editing: Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576(7785):149-157.

7. Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS, Essletzbichler P, Volz SE, Joung J, van der Oost J, Regev A, Koonin EV, Zhang F. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell. 2015;163(3):759-771.

8. Gootenberg JS, Abudayyeh OO, Lee JW, Essletzbichler P, Dy AJ, Joung J, Verdine V, Donghia N, Daringer NM, Freije CA, Myhrvold C, Bhattacharyya RP, Livny J, Regev A, Koonin EV, Hung DT, Sabeti PC, Collins JJ, Zhang F. Nucleic acid detection with CRISPR-Cas13a/C2c2. Science. 2017;356(6336):438-442.

9. Whiteley AR, Fitzpatrick SW, Funk WC, Tallmon DA.Genetic rescue to the rescue. Trends Ecol Evol. 2015;30(1):42-49.

10. Wisely SM, Ryder OA, Santymire RM, Engelhardt JF, Novak BJ. A roadmap for 21st-century genetic restoration: Gene pools, gene flow, and genetic rescue. Anim Conserv. 2015;18(3):213-222.

11. Ryder OA, Onuma M, Chemnick LG. Genetic rescue, cloning and the future of species conservation. J Hered. 2020;111(1):103-113.

12. Lynch M, Burger R, Butcher D, Gabriel W. The mutational meltdown in asexual populations.

J Hered. 1993;84(5):339-344.

13. Scheele BC, Pasmans F, Skerratt LF, Berger L, Martel A, Beukema W, Acevedo AA, Burrowes PA, Carvalho T, Catenazzi A, et al. Amphibian fungal panzootic causes catastrophic and ongoing loss of biodiversity. Science. 2019;363(6434):1459-1463.

14. Rollins RE, Echaubard P, Liu H, Raffel TR, Voyles J. Using genome editing to protect amphibians from chytrid fungus. Conserv Genet. 2022;23:1-15.

15. Esvelt KM, Smidler AL, Catteruccia F, Church GM. Concerning RNA-guided gene drives for the alteration of wild populations. eLife. 2014;3:e03401.

16. Burt A. Site-specific selfish genes as tools for the control and genetic engineering of natural populations. Proc R Soc Lond B Biol Sci. 2003;270(1518):921-928.

17. Campbell KJ, Beek J, Eason CT, Glen AS, Godwin J, Gould F, Holmes ND, Howald GR, Madden FM, Ponder JB, et al. The next generation of rodent eradications: Innovative technologies and tools to improve species specificity and increase their feasibility on islands.

Biol Conserv. 2015;185:47-58.

18. Kyrou K, Hammond AM, Galizi R, Kranjc N, Burt A, Beaghton AK, Nolan T, Crisanti A.

A CRISPR-Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nat Biotechnol. 2018;36(11):1062-1066.

19. Leitschuh CM, Kanavy D, Backus GA, Valdez RX, Serr M, Pitts EA, Threadgill D, Godwin J.

Developing gene drive technologies to eradicate invasive rodents from islands. Biol Invasions. 2018;20:1-15.

20. National Academies of Sciences, Engineering, and Medicine. Gene drives on the horizon: Advancing science, navigating uncertainty, and aligning research with public values.

Washington (DC): National Academies Press; 2016.

21. Shapiro B. How to clone a mammoth: The science of de-extinction.

Princeton (NJ): Princeton University Press; 2015.

22. Church GM. Editing the future of life. Science. 2018;360(6392):112.

23. Lynch VJ, Bedoya-Reina OC, Ratan A, Sulak M, Drautz-Moses DI, Perry GH, et al.

Elephantid genomes reveal the molecular bases of woolly mammoth adaptations to the Arctic. Cell Rep. 2015;12(2):217-228.

24. Zimov SA. Pleistocene Park: Return of the mammoth’s ecosystem. Science. 2005;308(5723):796-798.

25. Richmond DJ, Sinding C, Østman B. De-extinction: Ten steps to a restored species.

Br J Philos Sci. 2016;67(1):153-178.

26. Novak BJ. De-extinction. In: DellaSala DA, Goldstein MI, editors. Encyclopedia of the Anthropocene / Conservation Science. Amsterdam: Elsevier; 2018. p. 1-8.

27. Sandler RL. The ethics of reviving long-extinct species. Conserv Biol. 2014; 28(2):354-360.

28. Oye KA, Esvelt K, Appleton E, Catteruccia F, Church G, Kuiken T, Lightfoot SB, McNamara J, Smidler A, Collins JP. Regulating gene drives. Science. 2014;345(6197):626-628.

29. Callaway E. Gene drives: The story of a technology that could alter entire species.

Nature. 2016;534:164-166.

30. Meghani Z, Kuzma J. Regulating animals with gene drive systems: Lessons from the regulatory assessment of a genetically engineered mosquito. Health Care Anal. 2018;26(2):162-178.

31. Kuzma J. Procedural environmental justice and emerging technologies: The case of gene editing and gene drives. Land. 2019;8(8):129.

32. Fasig T. CRISPR and the legal framework for wildlife conservation. J Law Biosci. 2020;7(1):lsaa015.

33. Long KC, Alphey L, Annas GJ, Bloss CS, Campbell KJ, Champer J, et al. Core commitments for field trials of gene drive organisms. Science. 2020;370(6523):1417-1419.

34. Hartley S, Thizy D, Ledingham K, Coulibaly M, Diabaté A, Dicko B, et al.

Knowledge engagement in gene drive research for malaria control. PLoS One. 2020;15(4):e0230663.

35. Hammond A, Galizi R, Kyrou K, Simoni A, Siniscalchi C, Katsanos D, et al.

A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol. 2016;34(1):78-83.

36. KaramiNejadRanjbar M, Eckermann KN, Ahmed HMM, Sánchez C HM, Dippel S, Marshall JM, et al. Consequences of resistance evolution in a Cas9-based gene drive system. PLoS Genet. 2018;14(6):e1007428.

37. Marshall JM, Akbari OS. Can CRISPR-based gene drive be confined in the wild? A question for malaria control. Trends Parasitol. 2018;34(11):939-948.

38. Edgington MP, Alphey LS. Modelling the mutation and reversal of engineered underdominance gene drives. Genetics. 2017;207(2):420-431.

39. Akbari OS, Chen CH, Marshall JM, Huang H, Antoshechkin I, Hay BA.

A synthetic gene drive system for local, reversible modification and suppression of insect populations. Nat Commun. 2013;4:2308.

40. Oberhofer G, Ivy T, Hay BA. Cleave-and-rescue, a novel selfish genetic element and general strategy for gene drive. eLife. 2019;8:e41539.

41. Unckless RL, Clark AG, Messer PW. Evolution of resistance against CRISPR/Cas9 gene drive. Genetics. 2017;205(2):827-841.

42. Noble C, Adlam B, Church GM, Esvelt KM, Nowak MA. Current CRISPR gene drive systems are likely to be highly invasive in wild populations. eLife. 2018;7:e33423.

43. Prowse TAA, Adikusuma F, Cassey P, Thomas P, Ross JV. A Y-chromosome shredding gene drive for controlling pest vertebrate populations. eLife. 2019;8:e41873.

44. Noble C, Olejarz J, Esvelt KM, Church GM, Nowak MA. Evolutionary dynamics of CRISPR gene drives. Sci Adv. 2017;3(4):e1601964.

45. Reed FA. CRISPR/Cas9 gene drive: Growing pains for a new technology. Genetics. 2017;205(3):1037-1039.

46. Prowse TAA, Cassey P, Ross JV, Pfitzner C, Wittmann TA, Thomas P. A theory of resistance to CRISPR/Cas9 gene drive. Proc R Soc B Biol Sci. 2017;284:20170799.

47. Rode NO, Estoup A, Bourguet D, Courtier-Orgogozo V, Débarre F. Population structure and resistance evolution drive the spread of gene drives. Evolution. 2019;73(2):203-217.

48. Vella MR, Gunning CE, Lloyd AL, Gould F. Evaluating strategies for reversing CRISPR-Cas9 gene drives. Sci Rep. 2017;7:11038.

49. Li M, Yang T, Kandul NP, Bui M, Gamez S, Raban R, et al. Development of a confinable gene drive system in the human malaria mosquito. Nat Commun. 2020;11:1082.

50. Werren JH. Selfish genetic elements, genetic conflict, and evolutionary innovation.

Mol Ecol. 2011;20(8):1559-1571.

51. Zapletal J, Ergon T, Hovestadt T. Ecological stability and population suppression by gene drive. J Theor Biol. 2020;488:110126.

52. Johnson WE, Onorato DP, Roelke ME, Land ED, Cunningham M, Belden RC, et al.

Genetic restoration of the Florida panther. Science. 2010;329(5999):1641-1645.

53. Roelke ME, Martenson JS, O’Brien SJ. The consequences of demographic reduction and genetic depletion in the endangered Florida panther. Conserv Biol. 1993;7(4):777-786.

54. Pimm SL, Dollar L, Bass OL. The genetic rescue of the Florida panther.

Anim Conserv. 2006;9:115-122.

55. Veilleux HD, Ryu T, Donelson JM, van Herwerden L, Seridi L, Ghosheh Y, et al.

Molecular processes of reef fish responses to elevated temperature. Nat Clim Chang. 2015;5:551-555.

56. van Oppen MJH, Oliver JK, Putnam HM, Gates RD. Building coral reef resilience through assisted evolution. Proc Natl Acad Sci U S A. 2015;112(8):2307-2313.

57. Cleves PA, Strader ME, Bay LK, Pringle JR, Matz MV. CRISPR/Cas9-mediated genome editing in a reef-building coral. Proc Natl Acad Sci U S A. 2018;115(20):5235-5240.

58. Whyte J, Glover JD, Woodcock M, Brzeszczynska J, Taylor L, Sherman A, et al.

Fidelity of targeted gene modification in avian primordial germ cells. Nature. 2015;528:399-402.

59. Cooper CA, Challagulla A, Jenkins KA, Wise TG, O’Neil TE, Morris KR, et al.

Generation of gene-edited birds in the chicken using CRISPR/Cas9. Genetics. 2017;205(1):149-159.

60. Chan KY, Jang MJ, Yoo BB, Greenbaum A, Ravi N, Wu WL, et al. Engineered AAVs for efficient noninvasive gene delivery to the central nervous system.

Nat Neurosci. 2017;20:1172-1179.

61. Deverman BE, Pravdo PL, Simpson BP, Kumar SR, Chan KY, Banerjee A, et al.

Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain. Nat Biotechnol. 2016;34:204-209.

62. Redford KH, Adams W, Carlson RH, Mace GM, Ceccarelli B.

Synthetic biology and conservation of nature: Wicked problems and wicked solutions.

PLoS Biol. 2013;11(4):e1001530.

63. Piaggio AJ, Segelbacher G, Seddon PJ, Alphey L, Bennett EL, Carlson RH, et al.

Is it time for synthetic biology in conservation? Trends Ecol Evol. 2017;32(2):97-107.

64. Webber BL, Raghu S, Edwards OR. Is CRISPR-based gene drive a biocontrol silver bullet or global conservation threat? Proc Natl Acad Sci U S A. 2015;112(34):10565-10567.

65. Thomas MA, Roemer GW, Donlan CJ, Dickson BG, Matocq M, Malaney JL.

Gene tweaking for conservation. Nature. 2013;501:485-486.

66. Whittle CA, Extavour CG. Evolutionary genomics of small populations: Trends and conservation implications. J Hered. 2015;106(S1):1-11.

67. Kosch TA, Silva CN, Brannelly LA, Roberts AA, Lau Q, Berger L, et al.

Genetic editing of amphibians: Lessons learned from the chytrid fungus crisis. Front Conserv Sci. 2023;4:1123405.

68. Esvelt KM, Gemmell NJ. Conservation demands safe gene drive. PLoS Biol. 2017;15(11):e2003850.

69. Min J, Smidler AL, Noble C, Olejarz J, Buchanan J, Esvelt KM. Harnessing gene drive for the conservation of island species. Front Ecol Environ. 2021;19(8):463-471.

70. Champer J, Buchman A, Akbari OS. Cheating evolution: Engineering gene drives to manipulate wild populations. Nat Rev Genet. 2018;19(3):143-159.

71. National Academies of Sciences, Engineering, and Medicine. Forest health and biotechnology: Possibilities and considerations.Washington (DC): National Academies Press; 2019.

72. Buchman A, Gamez S, Li M, Antoshechkin I, Li HH, Wang HW, et al.

Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs. Proc Natl Acad Sci U S A. 2019;116(9):3656-3661.

73. Adolphs J, Heppell S, Dieckmann U. Evolutionary rescue in vertebrates: Modeling the CRISPR-Cas9 intervention threshold. Ecol Model. 2020;431:109158.

74. Bull JJ, Malik HS. The many faces of gene drive. Genetics. 2017;207(2):413-418.

75. Burt A, Crisanti A, Messer PW, Church GM. Gene drive: Evolved and synthetic.

ACS Chem Biol. 2018;13(2):343-351.

76. DiCarlo JE, Chavez A, Dietz SL, Esvelt KM, Church GM. Safeguarding CRISPR-Cas9 gene drive experiments in yeast. Nat Biotechnol. 2015;33(12):1250-1255.

77. Grunwald HA, Gantz VM, Poplawski G, Xu XS, Bier E, Cooper KL. Super-Mendelian inheritance mediated by CRISPR-Cas9 in the female mouse germline.

Nature. 2019;566:105-109.

78. Rode NO, Courtier-Orgogozo V, Débarre F. Can we use gene drive to control invasive populations on islands? Evolution. 2020;74(11):2441-2453.

79. Wang GH, Gamez S, Raban RR, Marshall JM, Alphey L, Li M. Symbiont-mediated gene drive in insects. Nat Commun. 2021;12:1-11.

80. Braverman AW. The ecological and ethical landscapes of de-extinction. Conserv Biol. 2022;36:e13885.

81. Cotter CT, O’Brien SJ. Genetic engineering and the rescue of rare alleles in fragmented carnivore populations. Front Genet. 2021;12:654122.

82. Giese B, von Gleich A. Biosafety of gene drives: A review of current risk-assessment protocols. Environ Sci Eur. 2019;31:1-15.

83. Taitingfong RI. Island sovereignty, Indigenous rights, and the governance of gene drive. New Genet Soc. 2019;38(4):341-359.

84. Smidler AL, Terenzi O, Soichot J, Levashina EA, Marois E. A framework for the evaluation of gene drive. Nat Commun. 2020;11:1-11.

85. Sudweeks J, Blondel DV, Campbell KJ, Dhole S, Lloyd AL. Locally fixed alleles: A method to localize gene drive to island populations. Evol Appl. 2021;14(4):1122-1134.

86. Onuma M, Ryder OA. Genome resource banks and the restoration of species diversity. J Hered. 2021;112(1):50-60.

87. Finn JD, Smith AR, Patel MC, Shaw L, Youniss MR, van Heteren J, et al. A single administration of CRISPR-Cas9 lipid nanoparticles achieves robust and persistent in vivo genome editing. Cell Rep. 2018;22:2227-2235.

88. Gantz VM, Bier E. The dawn of active genetics. Bioessays. 2016;38(1):50-63.

89. Rydberge J, Simon S. International governance and the Nagoya Protocol in the age of gene drive. Mar Policy. 2022;136:104905.

Downloads

Published

2026-02-25

Issue

Section

Articles

Similar Articles

<< < 18 19 20 21 22 23 24 25 26 27 > >> 

You may also start an advanced similarity search for this article.