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Viral- and Non-viral-Based Hybrid Vectors for Gene Therapy

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Gene and Cell Therapy: Biology and Applications

Abstract

Gene therapy offers a great potential for the treatment of genetic diseases as well as acquired diseases by means of delivering therapeutic nucleic acids inside the cell. To deliver nucleic acids, broadly two strategies have been employed by using viral vectors and non-viral vectors. The viral vectors exhibited high transduction efficacy both in vitro and in vivo. The non-viral vectors composed of mainly cationic polymers and lipids which provide efficient condensing capability against negatively charged nucleic acids and low cytotoxicity. Till date, >2300 clinical trials for gene therapy are going on worldwide, approximately 70% using viral vectors and remaining with non-viral vectors. The immunogenicity, non-targeting abilities are the biggest hurdles in terms of safety and efficiency for successful therapy with these vectors. These two classes of vectors have their own advantages as well as disadvantages which hinder their therapeutic endpoint in clinical trials. Now, researchers have made attempts to form virus encapsulated in chemical vectors which are called as hybrid vectors. These hybrid vectors have immense potential to evade host immune system by masking the immunogenic epitopes present on viral vectors. The molecules or scaffold which is used for encapsulating virus enhance their targeting ability and sustained release to targeted tissue. The hybrid vectors, combination of viral and chemical vectors, form a new class of gene delivery vectors which overcome the limitations of each vector and simultaneously augment desirable features such as targeting ability, low immunogenicity, cytotoxicity, higher payload, and ability to deliver more than one transgene. The hybrid vectors should retain characteristics of the each vector in order to achieve optimal tissue targeting and gene delivery with minimal toxicity. To achieve therapeutic endpoint with the hybrid vectors, development of such hybrid vectors requires extensive understanding of physicochemical properties after coating virus with chemical analogues and their optimal ratio as well. These aspects will be discussed in this chapter.

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Authors and Affiliations

  1. Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, India

    Manohar Mahato & Praveen Kumar Vemula

  2. Department of Biological Sciences and Bioengineering, IIT-Kanpur, Kanpur, UP, India

    Giridhara R. Jayandharan

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  1. Manohar Mahato
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  2. Giridhara R. Jayandharan
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  3. Praveen Kumar Vemula
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Correspondence to Praveen Kumar Vemula .

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  1. Department of BSBE, IIT-Kanpur, Kanpur, Uttar Pradesh, India

    Giridhara R. Jayandharan

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Mahato, M., Jayandharan, G.R., Vemula, P.K. (2018). Viral- and Non-viral-Based Hybrid Vectors for Gene Therapy. In: Jayandharan, G. (eds) Gene and Cell Therapy: Biology and Applications. Springer, Singapore. https://doi.org/10.1007/978-981-13-0481-1_4

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