Adeno-Associated Virus (AAV) Versus Immune Response
Decades ago, Friedmann and Roblin postulated several barriers to gene therapy, including tissue targeting, delivery across the blood⁻brain barrier (BBB), and host immune responses. These issues remain pertinent till today. Since then, several advances have been made in elucidating structur...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-01-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/11/2/102 |
| _version_ | 1818993572252221440 |
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| author | Joseph Rabinowitz Ying Kai Chan Richard Jude Samulski |
| author_facet | Joseph Rabinowitz Ying Kai Chan Richard Jude Samulski |
| author_sort | Joseph Rabinowitz |
| collection | DOAJ |
| description | Decades ago, Friedmann and Roblin postulated several barriers to gene therapy, including tissue targeting, delivery across the blood⁻brain barrier (BBB), and host immune responses. These issues remain pertinent till today. Since then, several advances have been made in elucidating structures of adeno-associated virus (AAV) serotypes, antibody epitopes, and ways to modify antibody-binding sites. AAVs capsid has also been engineered to re-direct tissue tropism, reduce ubiquitination, and promote passage across the BBB. Furthermore, the use of high(er) dose recombinant AAV (rAAV) has been accompanied by a better understanding of immune responses in both experimental animals and early clinical trials, and novel work is being performed to modulate the immune response. While the immune responses to rAAV remains a major challenge in translating experimental drugs to approved medicine, and will likely require more than a single solution, we now better understand the hurdles to formulate and test experimental solutions to surmount them. |
| first_indexed | 2024-12-20T20:44:11Z |
| format | Article |
| id | doaj.art-af708c1f37e5433fbb3597b60f74f3d9 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-20T20:44:11Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-af708c1f37e5433fbb3597b60f74f3d92022-12-21T19:27:05ZengMDPI AGViruses1999-49152019-01-0111210210.3390/v11020102v11020102Adeno-Associated Virus (AAV) Versus Immune ResponseJoseph Rabinowitz0Ying Kai Chan1Richard Jude Samulski2Senior Director of Capsid Development, Rare Disease Research Unit, Pfizer Inc., 7030 Kit Creek Road, Morrisville, NC 27560, USADepartment of Genetics, Harvard Medical School, Boston, MA 02115, USADepartment of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADecades ago, Friedmann and Roblin postulated several barriers to gene therapy, including tissue targeting, delivery across the blood⁻brain barrier (BBB), and host immune responses. These issues remain pertinent till today. Since then, several advances have been made in elucidating structures of adeno-associated virus (AAV) serotypes, antibody epitopes, and ways to modify antibody-binding sites. AAVs capsid has also been engineered to re-direct tissue tropism, reduce ubiquitination, and promote passage across the BBB. Furthermore, the use of high(er) dose recombinant AAV (rAAV) has been accompanied by a better understanding of immune responses in both experimental animals and early clinical trials, and novel work is being performed to modulate the immune response. While the immune responses to rAAV remains a major challenge in translating experimental drugs to approved medicine, and will likely require more than a single solution, we now better understand the hurdles to formulate and test experimental solutions to surmount them.https://www.mdpi.com/1999-4915/11/2/102rAAVimmune responserare diseases |
| spellingShingle | Joseph Rabinowitz Ying Kai Chan Richard Jude Samulski Adeno-Associated Virus (AAV) Versus Immune Response Viruses rAAV immune response rare diseases |
| title | Adeno-Associated Virus (AAV) Versus Immune Response |
| title_full | Adeno-Associated Virus (AAV) Versus Immune Response |
| title_fullStr | Adeno-Associated Virus (AAV) Versus Immune Response |
| title_full_unstemmed | Adeno-Associated Virus (AAV) Versus Immune Response |
| title_short | Adeno-Associated Virus (AAV) Versus Immune Response |
| title_sort | adeno associated virus aav versus immune response |
| topic | rAAV immune response rare diseases |
| url | https://www.mdpi.com/1999-4915/11/2/102 |
| work_keys_str_mv | AT josephrabinowitz adenoassociatedvirusaavversusimmuneresponse AT yingkaichan adenoassociatedvirusaavversusimmuneresponse AT richardjudesamulski adenoassociatedvirusaavversusimmuneresponse |