Preview

Uchenye Zapiski Kazanskogo Universiteta Seriya Estestvennye Nauki

Advanced search

Biodistribution Analysis of Adeno-Associated Viral Vectors of Serotypes 9 and rh.10 Encoding Arylsulfatase A Following Prior Immunization with Serotype 9 in Pigs

https://doi.org/10.26907/2542-064X.2024.4.683-703

Abstract

Lysosomal storage diseases are a group of inherited disorders caused by lysosomal dysfunction, impairing cellular metabolic enzymes, signaling pathways, and other biological processes. Among them is metachromatic leukodystrophy (MLD) associated with arylsulfatase A (ARSA) deficiency, which leads to the accumulation of sulfatides and the destruction of myelin sheaths in the nervous system. This study evaluates the therapeutic efficacy of adeno-associated viruses (AAVs) in treating neurodegenerative diseases such as MLD. The biodistribution and safety of AAV9-ARSA and AAVrh.10-ARSA vectors following prior immunization in pigs were shown. The immune aspects of AAV-based gene therapy were outlined. Its potential efficacy and durability limitations were discussed.

About the Authors

A. I. Mullagulova
Kazan Federal University
Russian Federation

Kazan, 420008 



A. A. Shaimardanova
Kazan Federal University
Russian Federation

Kazan, 420008 



Ya. O. Mukhamedshina
Kazan Federal University; Republican Clinical Hospital of Tatarstan
Russian Federation

Kazan, 420008 

Kazan, 420064 



V. V. Solovyeva
Kazan Federal University
Russian Federation

Kazan, 420008 



A. Ibrahim
Kazan Federal University
Russian Federation

Kazan, 420008 



A. A. Rizvanov
Kazan Federal University; Tatarstan Academy of Sciences
Russian Federation

Kazan, 420008

Kazan, 420111 



References

1. Platt F.M., d’Azzo A., Davidson B.L., Neufeld E.F., Tifft C.J. Lysosomal storage diseases. Nat. Rev. Dis. Primers, 2018, vol. 4, no. 1, art. 27. https://doi.org/10.1038/s41572-018-0025-4.

2. Shaimardanova A.A., Chulpanova D.S., Solovyeva V.V., Mullagulova A.I., Kitaeva K.V., Rizvanov A.A. New therapeutic strategies for the treatment of metachromatic leukodystrophy. Genes & Cells, 2020, vol. 15, no. 2, pp. 41–50. https://doi.org/10.23868/202004023. (In Russian)

3. Marcus J., Honigbaum S., Shroff S., Honke K., Rosenbluth J., Dupree J.L. Sulfatide is essential for the maintenance of CNS myelin and axon structure. Glia, 2006, vol. 53, no. 4, pp. 372–381. https://doi.org/10.1002/glia.20292.

4. Lamichhane A., Rocha Cabrero F. Metachromatic Leukodystrophy. Treasure Island, FL, StatPearls Publ., 2023.

5. Shaimardanova A.A., Chulpanova D.S., Solovyeva V.V., Mullagulova A.I., Kitaeva K.V., Allegrucci C., Rizvanov A.A. Metachromatic leukodystrophy: Diagnosis, modeling, and treatment approaches. Front. Med., 2020, vol. 7, art. 576221. https://doi.org/10.3389/fmed.2020.576221.

6. Van Rappard D.F., Boelens J.J., Wolf N.I. Metachromatic leukodystrophy: Disease spectrum and approaches for treatment. Best Pract. Res., Clin. Endocrinol. Metab., 2015, vol. 29, no. 2, pp. 261–273. https://doi.org/10.1016/j.beem.2014.10.001.

7. Beerepoot S., Nierkens S., Boelens J.J., Lindemans C., Bugiani M., Wolf N.I. Peripheral neuropathy in metachromatic leukodystrophy: Current status and future perspective. Orphanet J. Rare Dis., 2019, vol. 14, no. 1, art. 240. https://doi.org/10.1186/s13023-019-1220-4.

8. Smith N.J., Marcus R.E., Sahakian B.J., Kapur N., Cox T.M. Haematopoietic stem cell transplantation does not retard disease progression in the psycho-cognitive variant of late-onset metachromatic leukodystrophy. J. Inherited Metab. Dis., 2010, vol. 33, no. S3, pp. 471–475. https://doi.org/10.1007/s10545-010-9240-1.

9. Matthes F., Stroobants S., Gerlach D., Wohlenberg C., Wessig C., Fogh J., Gieselmann V., Eckhardt M., D’Hooge R., Matzner U. Efficacy of enzyme replacement therapy in an aggravated mouse model of metachromatic leukodystrophy declines with age. Hum. Mol. Genet., 2012, vol. 21, no. 11, pp. 2599–2609. https://doi.org/10.1093/hmg/dds086.

10. Fumagalli F., Calbi V., Natali Sora M. G., Sessa M., Baldoli C., Rancoita P.M.V., Ciotti F., Sarzana M., Fraschini M., Zambon A.A., Acquati S., Redaelli D., Attanasio V., Miglietta S., De Mattia F., Barzaghi F., Ferrua F., Migliavacca M., Tucci F., Gallo V., Del Carro U., Canale S., Spiga I., Lorioli L., Recupero S., Fratini E.S., Morena F., Silvani P., Calvi M.R., Facchini M., Locatelli S., Corti A., Zancan S., Antonioli G., Farinelli G., Gabaldo M., Garcia-Segovia J., Schwab L.C., Downey G.F., Filippi M., Cicalese M.P., Martino S., Di Serio C., Ciceri F., Bernardo M.E., Naldini L., Biffi A., Aiuti A. Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: Long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access. Lancet, 2022, vol. 399, no. 10322, pp. 372–383. https://doi.org/10.1016/S0140-6736(21)02017-1.

11. Hocquemiller M., Giersch L., Audrain M., Parker S., Cartier N. Adeno-associated virusbased gene therapy for CNS diseases. Hum. Gene Ther., 2016, vol. 27, no. 7, pp. 478–496. https://doi.org/10.1089/hum.2016.087.

12. Cearley C.N., Wolfe J.H. Transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and Rh10 in the mouse brain. Mol. Ther., 2006, vol. 13, no. 3, pp. 528–537. https://doi.org/10.1016/j.ymthe.2005.11.015.

13. Miyake N., Miyake K., Asakawa N., Yamamoto M., Shimada T. Long-term correction of biochemical and neurological abnormalities in MLD mice model by neonatal systemic injection of an AAV serotype 9 vector. Gene Ther., 2014, vol. 21, no. 4, pp. 427–433. https://doi.org/10.1038/gt.2014.17.

14. Mullagulova A., Shaimardanova A., Solovyeva V., Mukhamedshina Y., Chulpanova D., Kostennikov A., Issa S., Rizvanov A. Safety and efficacy of intravenous and intrathecal delivery of AAV9-mediated ARSA in minipigs. Int. J. Mol. Sci., 2023, vol. 24, no. 11, art. 9204. https://doi.org/10.3390/ijms24119204.

15. Piguet F., Sondhi D., Piraud M., Fouquet F., Hackett N.R., Ahouansou O., Vanier M.-T., Bieche I., Aubourg P., Crystal R.G., Cartier N., Sevin C. Correction of brain oligodendrocytes by AAVrh.10 intracerebral gene therapy in metachromatic leukodystrophy mice. Hum. Gene Ther., 2012, vol. 23, no. 8, pp. 903–914. https://doi.org/10.1089/hum.2012.015.

16. Rosenberg J.B., Chen A., De B.P., Dyke J.P., Ballon D.J., Monette S., Ricart Arbona R.J., Kaminsky S.M., Crystal R.G., Sondhi D. Safety of direct intraparenchymal AAVrh.10-mediated central nervous system gene therapy for metachromatic leukodystrophy. Hum. Gene Ther., 2021, vol. 32, nos. 11–12, pp. 563–580. https://doi.org/10.1089/hum.2020.269.

17. Newman S., Rupar T. Viral vector therapy as a therapeutic option for peripheral nerve disease associated with metachromatic leukodystrophy. Eur. J. Hum. Genet., 2019, vol. 27, no. S2, p. 1134.

18. Whitehead M., Osborne A., Yu-Wai-Man P., Martin K. Humoral immune responses to AAV gene therapy in the ocular compartment. Biol. Rev., 2021, vol. 96, no. 4, pp. 1616–1644. https://doi.org/10.1111/brv.12718.

19. Nidetz N.F., McGee M.C., Tse L.V., Li C., Cong L., Li Y., Huang W. Adeno-associated viral vectormediated immune responses: Understanding barriers to gene delivery. Pharmacol. Ther., 2020, vol. 207, art. 107453. https://doi.org/10.1016/j.pharmthera.2019.107453.

20. Rivière C., Danos O., Douar A.M. Long-term expression and repeated administration of AAV type 1, 2 and 5 vectors in skeletal muscle of immunocompetent adult mice. Gene Ther., 2006, vol. 13, no. 17, pp. 1300–1308. https://doi.org/10.1038/sj.gt.3302766.

21. Sinn P.L., Burnight E.R., McCray P.B., Jr. Progress and prospects: Prospects of repeated pulmonary administration of viral vectors. Gene Ther., 2009, vol. 16, no. 9, pp. 1059–1065. https://doi.org/10.1038/gt.2009.87.

22. Louis Jeune V., Joergensen J.A., Hajjar R.J., Weber T. Pre-existing anti-adeno-associated virus antibodies as a challenge in AAV gene therapy. Hum. Gene Ther. Methods, 2013, vol. 24, no. 2, pp. 59–67. https://doi.org/10.1089/hgtb.2012.24.

23. Kruzik A., Fetahagic D., Hartlieb B., Dorn S., Koppensteiner H., Horling F.M., Scheiflinger F., Reipert B.M., de la Rosa M. Prevalence of anti-adeno-associated virus immune responses in international cohorts of healthy donors. Mol. Ther. – Methods Clin. Dev., 2019, vol. 14, pp. 126–133. https://doi.org/10.1016/j.omtm.2019.05.014.

24. Matzner U., Hartmann D., Lüllmann-Rauch R., Coenen R., Rothert F., Månsson J.-E., Fredman P., D’Hooge R., De Deyn P.P., Gieselmann V. Bone marrow stem cell-based gene transfer in a mouse model for metachromatic leukodystrophy: Effects on visceral and nervous system disease manifestations. Gene Ther., 2002, vol. 9, no. 1, pp. 53–63. https://doi.org/10.1038/sj.gt.3301593.

25. Biffi A., Capotondo A., Fasano S., del Carro U., Marchesini S., Azuma H., Malaguti M.C., Amadio S., Brambilla R., Grompe M., Bordignon C., Quattrini A., Naldini L. Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in mice. J. Clin. Invest., 2006, vol. 116, no. 11, pp. 3070–3082. https://doi.org/10.1172/JCI28873.

26. Pupo A., Fernández A., Low S.H., François A., Suárez-Amarán L., Samulski R.J. AAV vectors: The Rubik’s cube of human gene therapy. Mol. Ther., 2022, vol. 30, no. 12, pp. 3515–3541. https://doi.org/10.1016/j.ymthe.2022.09.015.

27. Pillay S., Carette J.E. Host determinants of adeno-associated viral vector entry. Curr. Opin. Virol., 2017, vol. 24, pp. 124–131. https://doi.org/10.1016/j.coviro.2017.06.003.

28. Zhang H., Yang B., Mu X., Ahmed S.S., Su Q., He R., Wang H., Mueller C., Sena-Esteves M., Brown R., Xu Z., Gao G. Several rAAV vectors efficiently cross the blood-brain barrier and transduce neurons and astrocytes in the neonatal mouse central nervous system. Mol. Ther., 2011, vol. 19, no. 8, pp. 1440–1448. https://doi.org/10.1038/mt.2011.98.

29. Tanguy Y., Biferi M.G., Besse A., Astord S., Cohen-Tannoudji M., Marais T., Barkats M. Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice. Front. Mol. Neurosci., 2015, vol. 8, art. 36. https://doi.org/10.3389/fnmol.2015.00036.

30. Saraiva J., Nobre R.J., de Almeida L.P. Gene therapy for the CNS using AAVs: The impact of systemic delivery by AAV9. J. Controlled Release, 2016, vol. 241, pp. 94–109. https://doi.org/10.1016/j.jconrel.2016.09.011.

31. Miyake N., Miyake K., Sakai A., Yamamoto M., Suzuki H., Shimada T. Treatment of adult metachromatic leukodystrophy model mice using intrathecal administration of type 9 AAV vector encoding arylsulfatase A. Sci. Rep., 2021, vol. 11, no. 1, art. 20513. https://doi.org/10.1038/s41598-021-99979-2.

32. Audouard E., Oger V., Meha B., Cartier N., Sevin C., Piguet F. Complete correction of brain and spinal cord pathology in metachromatic leukodystrophy mice. Front. Mol. Neurosci., 2021, vol. 14, art. 677895. https://doi.org/10.3389/fnmol.2021.677895.

33. Petry H., Brooks A., Orme A., Wang P., Liu P., Xie J., Kretschmer P., Qian H.S., Hermiston T.W., Harkins R.N. Effect of viral dose on neutralizing antibody response and transgene expression after AAV1 vector re-administration in mice. Gene Ther., 2008, vol. 15, no. 1, pp. 54–60. https://doi.org/10.1038/sj.gt.3303037.

34. Manno C.S., Pierce G.F., Arruda V.R., Glader B., Ragni M., Rasko J.J.E., Ozelo M.C., Hoots K., Blatt P., Konkle B., Dake M., Kaye R., Razavi M., Zajko A., Zehnder J., Rustagi P., Nakai H., Chew A., Leonard D., Wright J.F., Lessard R.R., Sommer J.M., Tigges M., Sabatino D., Luk A., Jiang H., Mingozzi F., Couto L., Ertl H.C., High K.A., Kay M.A. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat. Med., 2006, vol. 12, no. 3, pp. 342–347. https://doi.org/10.1038/nm1358.

35. Li C., Samulski R.J. Engineering adeno-associated virus vectors for gene therapy. Nat. Rev. Genet., 2020, vol. 21, no. 4, pp. 255–272. https://doi.org/10.1038/s41576-019-0205-4.

36. Vardas E., Kaleebu P., Bekker L.-G., Hoosen A., Chomba E., Johnson P.R., Anklesaria P., Birungi J., Barin B., Boaz M., Cox J., Lehrman J., Stevens G., Gilmour J., Tarragona T., Hayes P., Lowenbein S., Kizito E., Fast P., Heald A.E., Schmidt C. A phase 2 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 vaccine based on adeno-associated virus. AIDS. Res. Hum. Retroviruses, 2010, vol. 26, no. 8, pp. 933–942. https://doi.org/10.1089/aid.2009.024.

37. Bennett J., Wellman J., Marshall K.A., McCague S., Ashtari M., DiStefano-Pappas J., Elci O.U., Chung D.C., Sun J., Wright J.F., Cross D.R., Aravand P., Cyckowski L.L., Bennicelli J.L., Mingozzi F., Auricchio A., Pierce E.A., Ruggiero J., Leroy B.P., Simonelli F., High K.A., Maguire A.M. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: A follow-on phase 1 trial. Lancet, 2016, vol. 388, no. 10045, pp. 661–672. https://doi.org/10.1016/S0140-6736(16)30371-3.


Review

For citations:


Mullagulova A.I., Shaimardanova A.A., Mukhamedshina Ya.O., Solovyeva V.V., Ibrahim A., Rizvanov A.A. Biodistribution Analysis of Adeno-Associated Viral Vectors of Serotypes 9 and rh.10 Encoding Arylsulfatase A Following Prior Immunization with Serotype 9 in Pigs. Uchenye Zapiski Kazanskogo Universiteta Seriya Estestvennye Nauki. 2024;166(4):683–703. (In Russ.) https://doi.org/10.26907/2542-064X.2024.4.683-703

Views: 211


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2542-064X (Print)
ISSN 2500-218X (Online)