| 학회 |
한국화학공학회 |
| 학술대회 |
2011년 가을 (10/26 ~ 10/28, 송도컨벤시아) |
| 권호 |
17권 2호, p.1456 |
| 발표분야 |
생물화공 |
| 제목 |
Specific Insertions of Zinc Finger Domains into Gag-Pol Yields Engineered Retroviral Vectors with Selective Integration Properties |
| 초록 |
The clinical use of retroviruses as vectors raises the concerns of insertional mutagenesis and potential oncogenesis due to genomic integration preferences for transcriptional start sites (TSSs). We have developed retroviral vector systems with altered integration specificity by generating a library of viruses with zinc finger domain (ZFD) inserted at random positions throughout murine leukemia virusGag-Pol, then selecting for variants that are viable and exhibit selective integration properties. We found seven permissive ZFD insertion sites throughout Gag-Pol. Comprehensive genome integration analysis revealed that several ZFD insertions yielded retroviralvariants with integration patterns that did not favor TSSs. Furthermore,twovariantsstrikingly integrated primarily into four common sites out of 3.1x10^9 possible human genome locations (P=4.6x10^-29). Our findings demonstrate that insertion of DNA binding motifs intoGag-Pol can make considerable progress toward engineering safer retroviral vectors. |
| 저자 |
임광일1, Ryan Klimczak2, David Schaffer2
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| 소속 |
1숙명여대 의약과학과 / Univ. of California at Berkeley, 2Univ. of California at Berkeley |
| 키워드 |
Gene Therapy; Retroviral Vectors; Viral Library; Genomic Analysis
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| E-Mail |
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| 원문파일 |
초록 보기 |
